Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)

• ClinicalTrials.gov Identifier: NCT02728102
• Recruitment Status: Completed
• First Posted: April 5, 2016
• Results First Posted: September 9, 2021
• Last Update Posted: May 7, 2024
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: Blood and Marrow Transplant Clinical Trials Network; National Cancer Institute (NCI); National Marrow Donor Program
• Information provided by (Responsible Party): National Heart, Lung, and Blood Institute (NHLBI)

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma
• Interventions: Procedure: Tumor Cell Collection; Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Procedure: Leukapheresis; Biological: Myeloma vaccine; Drug: GM-CSF; Drug: Lenalidomide
• Enrollment: 203

Participant Flow

Recruitment Details

The study opened to accrual on July 25, 2016 and closed to accrual on October 12, 2018 with 203 participants enrolled from 18 participating centers. The final study database lock was done September 9, 2021.

Pre-assignment Details

Sixty-three participants dropped out of the study prior to randomization and 140 participants received a transplant and proceeded to randomization. The reasons for dropout include insufficient tumor cells collected (n=13), withdrew consent from study (n=12), ineligible to be randomized (n=8), disease progression prior to randomization (n=6), refused or did not make it to transplantation (n=10), physician decision (n=7), manufacturing failure (n=4), lost to follow up (n=2), and insurance (n=1).

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Period Title: Overall Study
Started	68	37	35
Completed	61	33	30
Not Completed	7	4	5
Reason Not Completed
Death	3	0	1
Withdrawal by Subject	0	2	3
Physician Decision	1	1	0
Investigational study drug permanently discontinued	3	1	0
Covid	0	0	1

Baseline Characteristics

Arm/Group Title		Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide	Total
Arm/Group Description		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.	Total of all reporting groups
Overall Number of Baseline Participants		68	37	35	140
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
		59.3; (41.6 to 70.2)	62.3; (44.2 to 70.2)	59.1; (35.2 to 70.9)	60.0; (35.2 to 70.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
	Female	27 39.7%	18 48.6%	18 51.4%	63 45.0%
	Male	41 60.3%	19 51.4%	17 48.6%	77 55.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
	Hispanic or Latino	4 5.9%	3 8.1%	4 11.4%	11 7.9%
	Not Hispanic or Latino	61 89.7%	33 89.2%	30 85.7%	124 88.6%
	Unknown or Not Reported	3 4.4%	1 2.7%	1 2.9%	5 3.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
	American Indian or Alaska Native	1 1.5%	0 0.0%	0 0.0%	1 0.7%
	Asian	2 2.9%	2 5.4%	0 0.0%	4 2.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	8 11.8%	2 5.4%	5 14.3%	15 10.7%
	White	54 79.4%	30 81.1%	28 80.0%	112 80.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	3 4.4%	3 8.1%	2 5.7%	8 5.7%
Karnofsky Performance Score (KPS) [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
	100	16 23.5%	7 18.9%	9 25.7%	32 22.9%
	90	29 42.6%	10 27.0%	14 40.0%	53 37.9%
	80	17 25.0%	15 40.5%	9 25.7%	41 29.3%
	70	6 8.8%	5 13.5%	3 8.6%	14 10.0%
		[1] Measure Description: KPS describes patient-perceived global quality of life and functioning on a scale of 0-100. 100: No evidence of disease; 90: Normal activity. Minor signs or symptoms of disease; 80: Normal activity with effort. Some signs or symptoms of disease; 70: Cares for self. Unable to continue normal activity; 60: Needs occasional assistance, but cares for most personal needs; 50: Needs considerable assistance and medical care; 40: Disabled. Needs special care and assistance; 30: Severely disabled. Hospital admission indicated; 20: Very sick. Active supportive therapy needed; 10: Moribund; 0: Dead
Disease Response at Randomization [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	68 participants	37 participants	35 participants	140 participants
	Stringent Complete Response (sCR)	11 16.2%	6 16.2%	4 11.4%	21 15.0%
	Complete Response (CR)	11 16.2%	9 24.3%	9 25.7%	29 20.7%
	Very Good Partial Response (VGPR)	37 54.4%	15 40.5%	17 48.6%	69 49.3%
	Partial Response (PR)	9 13.2%	7 18.9%	5 14.3%	21 15.0%
	Stable Response	0 0.0%	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Description: CR: no original monoclonal paraprotein, < 5% BM plasma cells, no lytic bone lesions increase, and no soft tissue plasmacytomas. sCR: CR, normal FLC ratio, and no clonal cells. PR: >= 50% serum monoclonal paraprotein decrease and 24 hr urinary monoclonal decrease, or >= 50% involved and uninvolved FLC decrease or a 50% decrease in involved FLC w/ 50% ratio decrease, or >= 50% BM plasma cells decrease, or >= 50% soft tissue plasmacytomas decrease. VGPR: PR, paraprotein decrease or >= 90% serum paraprotein decrease, and a 90% involved light chain decrease. SD: none of above and no progression.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With 1-year Response Rate of CR/sCR
Description	The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The primary analysis population includes all the randomized participants. Protocol defines primary analysis is to compare participants receiving vaccine vs those without vaccine. So no vaccine arms with or without GM-CSF are combined. Four participants withdrew consent to all study procedures before 1-year post-transplant. Of these, 2 cases on the Lenalidomide/GM-CSF arm and 2 cases on the Lenalidomide Alone arm. These participants were not evaluable for the primary endpoint and ERC confirmed.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	68
Measure Type: Number; Number (80% Confidence Interval); Unit of Measure: percentage of participants
	52.9; (44.5 to 61.3)	50.0; (41.6 to 58.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be described in the vaccine and no vaccine groups with 80% confidence intervals and compared between groups using a two-sample Z test comparing binomial proportions.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3657
	Comments	A one-sided significance level of 0.10 is used to assess whether the vaccine appears promising relative to control.
	Method	Z test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 80%; -8.8 to 14.6
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary analysis stratified on disease response prior to randomization between arms will be conducted using a Cochran-Mantel-Haenszel test, and a stratified odds ratio along with 80% confidence intervals will be estimated.
	Type of Statistical Test	Equivalence
	Comments	The stratified odds ratio is estimated with 80% confidence intervals.
Statistical Test of Hypothesis	P-Value	0.7461
	Comments	P-value is provided by Breslow-Day Test for Homogeneity of the Odds Ratios.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 80%; 0.70 to 2.03
	Estimation Comments	The Cochran-Mantel-Haenszel Odds Ratio estimate is for the Stratification. Stratum 1 is sCR/CR at Randomization. Stratum 2 is VGPR/PR/Stable Response at Randomization.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary pairwise analysis of CR/sCR rates comparing the vaccine arm to Lenalidomide/GM-CSF arm at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide/GM-CSF arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
Statistical Test of Hypothesis	P-Value	0.2429
	Comments	[Not Specified]
	Method	Z test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 80%; -6.4 to 20.6
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary pairwise analysis of CR rates comparing the vaccine arm to Lenalidomide alone arm at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide alone arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.
Statistical Test of Hypothesis	P-Value	0.4397
	Comments	[Not Specified]
	Method	Z test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 80%; -15.6 to 12.4
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Participants Response to Treatment
Description	A participant's disease status is evaluated based on the International Uniform Response Criteria per protocol. Before disease progression (PD), all disease classifications including stringent complete response (sCR), complete response (CR), very good partial remission (VGPR), partial response (PR), stable disease (SD) are relative to participant's disease status at study entry. Disease status is 'Not Evaluable' when disease assessment is not required, or disease status is missing.
Time Frame	6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapy

Outcome Measure Data

Analysis Population Description

Analysis Population includes transplanted participants.

Arm/Group Title		Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed		68	37	35
Measure Type: Count of Participants; Unit of Measure: Participants
Disease Status at 6 Months	Stringent Complete Response (sCR)	12 17.6%	9 24.3%	8 22.9%
	Complete Response (CR)	17 25.0%	8 21.6%	10 28.6%
	Very Good Partial Remission (VGPR)	28 41.2%	12 32.4%	13 37.1%
	Partial Response (PR)	5 7.4%	5 13.5%	2 5.7%
	Stable Disease (SD)	2 2.9%	1 2.7%	0 0.0%
	Progression (PD)	0 0.0%	0 0.0%	0 0.0%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	4 5.9%	2 5.4%	2 5.7%
Disease Status at 12 Months	Stringent Complete Response (sCR)	18 26.5%	8 21.6%	9 25.7%
	Complete Response (CR)	18 26.5%	8 21.6%	9 25.7%
	Very Good Partial Remission (VGPR)	22 32.4%	12 32.4%	10 28.6%
	Partial Response (PR)	4 5.9%	7 18.9%	3 8.6%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	5 7.4%	0 0.0%	2 5.7%
	Dead	1 1.5%	0 0.0%	0 0.0%
	Not Evaluable	0 0.0%	2 5.4%	2 5.7%
Disease Status at 24 Months	Stringent Complete Response (sCR)	17 25.0%	7 18.9%	9 25.7%
	Complete Response (CR)	13 19.1%	6 16.2%	10 28.6%
	Very Good Partial Remission (VGPR)	15 22.1%	15 40.5%	3 8.6%
	Partial Response (PR)	6 8.8%	4 10.8%	2 5.7%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	2 2.9%	0 0.0%	0 0.0%
	Dead	2 2.9%	0 0.0%	1 2.9%
	Not Evaluable	13 19.1%	5 13.5%	10 28.6%
Disease Status at Cycle 3 (Day 57 Assessment)	Stringent Complete Response (sCR)	8 11.8%	9 24.3%	7 20.0%
	Complete Response (CR)	19 27.9%	5 13.5%	14 40.0%
	Very Good Partial Remission (VGPR)	35 51.5%	15 40.5%	11 31.4%
	Partial Response (PR)	5 7.4%	6 16.2%	2 5.7%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	0 0.0%	0 0.0%	0 0.0%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	1 1.5%	2 5.4%	1 2.9%
Disease Status at Cycle 6 (Day 141 Assessment)	Stringent Complete Response (sCR)	13 19.1%	7 18.9%	7 20.0%
	Complete Response (CR)	18 26.5%	7 18.9%	14 40.0%
	Very Good Partial Remission (VGPR)	28 41.2%	14 37.8%	10 28.6%
	Partial Response (PR)	6 8.8%	7 18.9%	2 5.7%
	Stable Disease (SD)	1 1.5%	0 0.0%	0 0.0%
	Progression (PD)	1 1.5%	0 0.0%	0 0.0%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	1 1.5%	2 5.4%	2 5.7%
Disease Status at Cycle 9 (Day 225 Assessment)	Stringent Complete Response (sCR)	16 23.5%	8 21.6%	9 25.7%
	Complete Response (CR)	17 25.0%	7 18.9%	15 42.9%
	Very Good Partial Remission (VGPR)	24 35.3%	13 35.1%	7 20.0%
	Partial Response (PR)	6 8.8%	7 18.9%	2 5.7%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	2 2.9%	0 0.0%	0 0.0%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	3 4.4%	2 5.4%	2 5.7%
Disease Status at Cycle 12 (Day 309 Assessment)	Stringent Complete Response (sCR)	18 26.5%	9 24.3%	9 25.7%
	Complete Response (CR)	18 26.5%	6 16.2%	10 28.6%
	Very Good Partial Remission (VGPR)	20 29.4%	13 35.1%	7 20.0%
	Partial Response (PR)	5 7.4%	7 18.9%	4 11.4%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	0 0.0%	0 0.0%	2 5.7%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	7 10.3%	2 5.4%	3 8.6%
Disease Status at Cycle 15 (Day 393 Assessment)	Stringent Complete Response (sCR)	18 26.5%	9 24.3%	9 25.7%
	Complete Response (CR)	17 25.0%	5 13.5%	13 37.1%
	Very Good Partial Remission (VGPR)	18 26.5%	11 29.7%	6 17.1%
	Partial Response (PR)	4 5.9%	7 18.9%	2 5.7%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	3 4.4%	0 0.0%	1 2.9%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	8 11.8%	5 13.5%	4 11.4%
Disease Status at Cycle 18 (Day 477 Assessment)	Stringent Complete Response (sCR)	20 29.4%	7 18.9%	7 20.0%
	Complete Response (CR)	16 23.5%	7 18.9%	13 37.1%
	Very Good Partial Remission (VGPR)	17 25.0%	14 37.8%	6 17.1%
	Partial Response (PR)	3 4.4%	6 16.2%	1 2.9%
	Stable Disease (SD)	2 2.9%	0 0.0%	0 0.0%
	Progression (PD)	1 1.5%	0 0.0%	1 2.9%
	Dead	0 0.0%	0 0.0%	0 0.0%
	Not Evaluable	9 13.2%	3 8.1%	7 20.0%
Disease Status at Cycle 21 (Day 561 Assessment)	Stringent Complete Response (sCR)	20 29.4%	6 16.2%	10 28.6%
	Complete Response (CR)	15 22.1%	5 13.5%	11 31.4%
	Very Good Partial Remission (VGPR)	14 20.6%	17 45.9%	6 17.1%
	Partial Response (PR)	5 7.4%	4 10.8%	1 2.9%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	2 2.9%	0 0.0%	0 0.0%
	Dead	1 1.5%	0 0.0%	0 0.0%
	Not Evaluable	11 16.2%	5 13.5%	7 20.0%
Disease Status at Cycle 24 (Day 654 Assessment)	Stringent Complete Response (sCR)	19 27.9%	6 16.2%	9 25.7%
	Complete Response (CR)	15 22.1%	7 18.9%	11 31.4%
	Very Good Partial Remission (VGPR)	14 20.6%	16 43.2%	6 17.1%
	Partial Response (PR)	6 8.8%	3 8.1%	1 2.9%
	Stable Disease (SD)	0 0.0%	0 0.0%	0 0.0%
	Progression (PD)	1 1.5%	1 2.7%	0 0.0%
	Dead	1 1.5%	0 0.0%	1 2.9%
	Not Evaluable	12 17.6%	4 10.8%	7 20.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9376
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4887
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5176
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between lenalidomide/GM-CSF arm and lenalidomide alone arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2461
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2530
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2213
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4930
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the lenalidomide/GM-CSF arm and lenalidomide alone arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6591
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6790
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3124
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7379
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the lenalidomide/GM-CSF arm and lenalidomide alone arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2379
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5353
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 12 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4417
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 24 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9450
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine arm and lenalidomide/GM-CSF arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1599
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine arm and lenalidomide alone arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8984
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between lenalidomide/GM-CSF arm and lenalidomide alone arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1757
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms
Description	The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm and the combined non-vaccine arms using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.7; (12 to 31.1)	11.8; (5.5 to 20.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.161
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With Myeloma Progression in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Myeloma Progression. The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	20.7; (12 to 31.1)	8.7; (2.2 to 21.0)	15.1; (5.4 to 29.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.116
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.519
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.387
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With Treatment-related Mortality (TRM)
Description	TRM is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for TRM. Patients alive without disease progression at last contact are considered censored for this event. TRM from time of randomization will be compared between vaccine and no-vaccine arms combined starting at time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0 to 0)	0; (0 to 0)

6. Secondary Outcome

Title	Percentage of Participants With Progression-Free Survival
Description	Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine and the combined non-vaccine arms using the log-rank test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	79.3; (67.6 to 87.2)	88.2; (77.8 to 93.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.168
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

7. Secondary Outcome

Title	Percentage of Participants With Progression-Free Survival in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Progression-Free Survival. Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	79.3; (67.6 to 87.2)	91.3; (75.5 to 97.1)	84.9; (67.5 to 93.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.120
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.519
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.387
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants With Overall Survival
Description	Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine and the combined non-vaccine arms from time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	97; (88.6 to 99.2)	98.5; (89.7 to 99.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of overall Survival between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.563
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

9. Secondary Outcome

Title	Percentage of Participants With Overall Survival in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Overall Survival. Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm from time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	97; (88.6 to 99.2)	100; (100 to 100)	96.9; (79.8 to 99.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	The null hypothesis is that there is no difference of overall Survival between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.308
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of overall Survival between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.990
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of overall Survival between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.303
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments	[Not Specified]

10. Secondary Outcome

Title	Number of Grade ≥ 3 Toxicities
Description	Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. All Grade ≥ 3 toxicities will be tabulated for treatment arms. Toxicities are categorized by organ system according to the CTCAE. Toxicities that involve multiple questions per organ system are combined in one category.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Unit of Measure: Toxicities
Auditory Disorders	1	0	0
Blood and Lymphatic Disorders	81	40	38
Cardiovascular Disorders	4	3	2
GI Disorders	15	4	2
General Disorders	5	2	2
Hepatobiliary/Pancreas Disorders	4	1	1
Immune System Disorders	2	0	0
Investigations	2	0	1
Metabolism and Nutrition Disorders	7	1	3
Musculoskeletal and Connective Tissue Disorders	1	1	2
Nervous System Disorders	14	5	1
Renal Disorders	1	0	2
Respiratory, Thoracic and Mediastinal Disorders	5	1	2
Skin and Subcutaneous Tissue Disorders	4	5	7
Vascular Disorders	6	11	3
Abnormal Liver Symptoms	0	1	0

11. Secondary Outcome

Title	Participants With Grade ≥ 3 Toxicities
Description	Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. The number of participants experiencing Grade ≥ 3 toxicity are displayed for the vaccine and non-vaccine arms separately. The proportion of participants experiencing Grade ≥ 3 toxicity are compared between the vaccine and non-vaccine arms combined.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Count of Participants; Unit of Measure: Participants
	53 77.9%	49 68.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of proportions of patients With Grade ≥ 3 Toxicities between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.189
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments	[Not Specified]

12. Secondary Outcome

Title	Number of Grade 2 and 3 Infections
Description	Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after randomization will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
Time Frame	2years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Unit of Measure: infections
Bacterial	10	3	6
Viral	14	6	14
Fungal	0	0	0
Other	1	0	1

13. Secondary Outcome

Title	Percentage of Participants With Grade 2 and 3 Infections
Description	Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine and the combined non-vaccine groups using the Gray's test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed	68	72
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	26.6; (16.7 to 37.6)	23.2; (14 to 33.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.82
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

14. Secondary Outcome

Title	Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Grade 2 and 3 infections. Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using the Gray's test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description:	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Overall Number of Participants Analyzed	68	37	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	26.6; (16.7 to 37.6)	14.2; (5.1 to 27.8)	32.6; (17.5 to 48.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide and GM-CSF
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.21
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.40
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.08
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments	[Not Specified]

15. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease (MRD)
Description	Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. Multichannel flow cytometry will be used to establish MRD based on the presence of malignant plasma cells that are CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The number of patients with MRD negative (MRD-) are described using frequencies at pre-randomization and 9th cycle post-randomization and compared between the vaccine arm with the no-vaccine arms combined.
Time Frame	Pre-randomization, Post-randomization at Cycle 9

Outcome Measure Data

Analysis Population Description

The randomized participants who had MRD assessment. Participants who did not have MRD assessment are not included in this analysis.

Arm/Group Title		Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description:		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Overall Number of Participants Analyzed		65	66
Measure Type: Count of Participants; Unit of Measure: Participants
Pre-randomization	Number Analyzed	65 participants	66 participants
		35 53.8%	31 47.0%
Post-randomization at Cycle 9	Number Analyzed	53 participants	59 participants
		38 71.7%	41 69.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of proportions of patients without Minimal Residual Disease between vaccine vs. non- vaccine arms
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.80
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments	[Not Specified]

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
All-Cause Mortality
	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	3/68 (4.41%)		0/37 (0.00%)		1/35 (2.86%)
Serious Adverse Events
	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/68 (2.94%)		3/37 (8.11%)		1/35 (2.86%)
Blood and lymphatic system disorders
NEUTROPENIC FEVER * 1	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
Cardiac disorders
ATRIAL FLUTTER * 1	0/68 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1
CONGESTIVE HEART FAILURE * 1	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
Investigations
PROLONGED QTC * 2	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
ELEVATE LIVER ENZYMES * 3	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
LIVER FUNCTION TESTS INCREASED * 4	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOMA * 1	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
Nervous system disorders
SYNCOPE * 1	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
1 Term from vocabulary, MedDRA 20.0-23.0; 2 Term from vocabulary, MedDRA 20.1; 3 Term from vocabulary, MedDRA 21.1; 4 Term from vocabulary, MedDRA 23.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.41%)		3/37 (8.11%)		3/35 (8.57%)
Cardiac disorders
ATRIAL FIBRILLATION * 2	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
Investigations
ELEVATED ALT * 2	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
INCREASED ALT > 3.0 X ULN * 3	0/68 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1
ELEVATED LFT * 4	0/68 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1
GRADE 2 TRANSAMINITIS * 4	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LENTIGO MALIGNA * 1	1/68 (1.47%)	1	0/37 (0.00%)	0	0/35 (0.00%)	0
PROSTATE CANCER * 2	0/68 (0.00%)	0	0/37 (0.00%)	0	1/35 (2.86%)	1
Vascular disorders
GRADE 2 DVT * 4	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
THROMBOEMBOLIC EVENT * 2	0/68 (0.00%)	0	1/37 (2.70%)	1	0/35 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; 2 Term from vocabulary, MedDRA 20.0-23.0; 3 Term from vocabulary, MedDRA 20.1; 4 Term from vocabulary, MedDRA 22.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Adam Mendizabal, PhD
• Organization: The Emmes Company
• Phone: 301-284-1798
• EMail: amendizabal@emmes.com

Publications:

Chung DJ, Shah N, Wu J, Logan B, Bisharat L, Callander N, Cheloni G, Anderson K, Chodon T, Dhakal B, Devine S, Somaiya Dutt P, Efebera Y, Geller N, Ghiasuddin H, Hematti P, Holmberg L, Howard A, Johnson B, Karagkouni D, Lazarus HM, Malek E, McCarthy P, McKenna D, Mendizabal A, Nooka A, Munshi N, O'Donnell L, Rapoport AP, Reese J, Rosenblatt J, Soiffer R, Stroopinsky D, Uhl L, Vlachos IS, Waller EK, Young JW, Pasquini MC, Avigan D. Randomized Phase II Trial of Dendritic Cell/Myeloma Fusion Vaccine with Lenalidomide Maintenance after Upfront Autologous Hematopoietic Cell Transplantation for Multiple Myeloma: BMT CTN 1401. Clin Cancer Res. 2023 Dec 1;29(23):4784-4796. doi: 10.1158/1078-0432.CCR-23-0235.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT02728102
• Other Study ID Numbers: BMT CTN 1401; U01HL069294 ( U.S. NIH Grant/Contract )
• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Results First Submitted: July 9, 2021
• Results First Posted: September 9, 2021
• Last Update Posted: May 7, 2024