Lenalidomide and Dexamethasone With or Without Thalidomide in Treating Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00098475

Recruitment Status : Active, not recruiting

First Posted : December 8, 2004

Results First Posted : January 22, 2014

Last Update Posted : May 16, 2024

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Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Conditions	DS Stage I Multiple Myeloma DS Stage II Multiple Myeloma DS Stage III Multiple Myeloma
Interventions	Drug: Dexamethasone Other: Laboratory Biomarker Analysis Drug: Lenalidomide Drug: Thalidomide
Enrollment	452

Participant Flow

Recruitment Details	The study opened on October 26, 2004 and was closed on June 1, 2007 with a total accrual of 452 patients enrolled from 6 groups and 77 institutions.
Pre-assignment Details


Arm/Group Title	Arm I (Lenalidomide, Dexamethasone)	Arm II (Lenalidomide, Low-dose Dexamethasone)	Arm III (Expansion; Lenalidomide, Dexamethasone, Aspirin)	Arm IV (Expansion; Lenalidomide, Dexamethasone, Coumadin)
Arm/Group Description	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...
Arm/Group Description	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles.	Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles.	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. After 4 cycles of treatment, patients may discontinue treatment or continue until progression.	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. After 4 cycles of treatment, patients may discontinue treatment. For patients continuing therapy beyond 4 cycles, coumadin was discontinued and aspirin was given instead.
Period Title: Step 1
Started	223	222	4	3
Treated	223	220	4	3
Eligible	214 ^[1]	208 ^[1]	4	3
Completed	52	49	0	0
Not Completed	171	173	4	3
Reason Not Completed
Progressive disease	33	35	2	1
Adverse Event	56	37	0	1
Death	8	5	0	1
Withdrawal by Subject	14	11	0	0
Physician Decision	5	2	0	0
Alternative therapy	31	43	1	0
Other disease	2	1	1	0
Never started treatment	0	2	0	0
Still on treatment as of this analysis	14	27	0	0
Knee surgery	1	0	0	0
Complications	1	0	0	0
Cannot comply due to other tx	0	1	0	0
Both patient and physician's decision	2	1	0	0
Incorrect disease assessment	2	0	0	0
Off treatment for > specified timeframe	1	1	0	0
Declining performance status	0	1	0	0
Insurance issue	0	1	0	0
Rising paraprotein	0	1	0	0
Referred to other physicians	0	1	0	0
Criteria to continue treatment not met	0	1	0	0
Misinterpretation of lab data	0	1	0	0
Patient fell with fracture	1	0	0	0
Not documented	0	1	0	0
[1] Some patients were considered eligible at registration but found ineligible in the analysis.
Period Title: Step 2
Started	5 ^[1]	15 ^[1]	0	0
Treated	4	14	0	0
Eligible	2 ^[2]	9 ^[2]	0	0
Completed	0	5	0	0
Not Completed	5	10	0	0
Reason Not Completed
Disease progression	1	4	0	0
Adverse Event	2	0	0	0
Withdrawal by Subject	0	2	0	0
Physician Decision	0	1	0	0
Alternative therapy	1	2	0	0
Never started treatment	1	1	0	0
[1] Step 2 treatment was an option but not required for patients who ended step 1 treatment. [2] Some patients were considered eligible at registration but found ineligible in the analysis.

Baseline Characteristics

Arm/Group Title		Arm I (Lenalidomide, Dexamethasone)	Arm II (Lenalidomide, Low-dose Dexamethasone)	Total
Arm/Group Description		Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...	Total of all reporting groups
Arm/Group Description		Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles. As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only. Toxicity data are available for both the first phase and the expansion phase.	Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles. As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only. Toxicity data are available for both the first phase and the expansion phase.	Total of all reporting groups
Overall Number of Baseline Participants		223	222	445
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	223 participants	222 participants	445 participants
		66 (36 to 87)	65 (35 to 85)	65 (35 to 87)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	223 participants	222 participants	445 participants
	Female	91 40.8%	101 45.5%	192 43.1%
	Male	132 59.2%	121 54.5%	253 56.9%

Outcome Measures

1.Primary Outcome


Title	Proportion of Patients With Objective Response (First Phase, Step 1)
Description	Objective response is defined as either complete response (CR) or part...
Description	Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response). As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only.
Time Frame	Assessed every 4 weeks for 16 weeks during Step 1

Outcome Measure Data

Analysis Population Description

Only eligible patients were included in this analysis.


Arm/Group Title	Arm I (Lenalidomide, Dexamethasone)	Arm II (Lenalidomide, Low-dose Dexamethasone)
Arm/Group Description:	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...
Arm/Group Description:	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles.	Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles.
Overall Number of Participants Analyzed	214	208
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Proportion of patients
	0.79 (0.729 to 0.842)	0.683 (0.615 to 0.745)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Lenalidomide, Dexamethasone), Arm II (Lenalidomide, Low-dose Dexamethasone)
	Comments	The study was designed to determine if a reduced dose of dexamethasone in combination with CC-5013 reduced toxicity rate without reducing response rate. The standard-dose response was expected to be 70%. The low dose would be deemed unacceptable if the difference in response rate between arms was >=15%. The null hypothesis was that response rates were equal and the alternative was that the low-dose response was no worse than 55%. The design had a 1-sided 0.10 type I error rate and 95% power.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	The low-dose response would be considered unacceptable if the difference in response rates was 15% or greater (the upper confidence limit exceeds the 15% acceptable difference) regardless of a decrease in toxicity rate.

Method of Estimation	Estimation Parameter	Difference in response rate between arms
	Estimated Value	0.107
	Confidence Interval	(2-Sided) 80% 0.052 to 0.162
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Proportion of Patients With Objective Response (First Phase, Step 2)
Description	Objective response is defined as either complete response (CR) or part...
Description	Objective response is defined as either complete response (CR) or partial response (PR). Patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow are considered to have CR. PR requires all the following: (1) ≥50% reduction in the level of the serum monoclonal paraprotein. (2) Reduction in 24-hour urinary light chain excretion either by ≥90% or to <200 mg. (3)For patients with non-secretory (or oligosecretory) myeloma only, a ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy must be documented. (4)50% reduction in size of soft tissue plasmacytoma (by radiography or clinical examination). (5) No increase in the number or size of lytic bone lesions (development of a compression fracture does not exclude response). As the expansion phase was a substudy terminated early with only 7 patients enrolled, the clinical results presented are mainly for the first phase only.
Time Frame	Assessed every 4 weeks for 16 weeks during Step 2

Outcome Measure Data

Analysis Population Description

Only eligible patients were included in this analysis.


Arm/Group Title	Arm I (Lenalidomide, Dexamethasone)	Arm II (Lenalidomide, Low-dose Dexamethasone)
Arm/Group Description:	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...
Arm/Group Description:	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles.	Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles.
Overall Number of Participants Analyzed	2	9
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Proportion of patients
	0 (0.0 to 0.842)	0 (0.0 to 0.336)

Adverse Events

Time Frame	Assessed every 4 weeks while on treatment and for 30 days after the end of treatment.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm I (Lenalidomide, Dexamethasone) Step 1	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 1	Arm I (Lenalidomide, Dexamethasone) Step 2	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 2	Arm III (Expansion; Lenalidomide, Dexamethasone, Aspirin)	Arm IV (Expansion; Lenalidomide, Dexamethasone, Coumadin)
Arm/Group Description	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...	Arm I patients with minimal respons...	Arm II patients with minimal respon...	Patients receive oral lenalidomide ...	Patients receive oral lenalidomide ...
Arm/Group Description	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles.	Patients receive oral lenalidomide and acetylsalicylic acid as in arm I and low-dose oral dexamethasone once daily on days 1, 8, 15, and 22. Patients with minimal response or no response after 4 cycles of treatment could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles.	Arm I patients with minimal response or no response after 4 cycles of treatment in Step 1 could register for Step 2 treatment with thalidomide and high-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1-4, 9-12, and 17-20 for 4 cycles.	Arm II patients with minimal response or no response after 4 cycles of treatment in Step 1 could register for Step 2 treatment with thalidomide and low-dose dexamethasone. Thalidomide was given orally once daily on days 1-28, and dexamethasone once daily on days 1, 8, 15, and 22 for 4 cycles.	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. After 4 cycles of treatment, patients may discontinue treatment or continue until progression.	Patients receive oral lenalidomide once daily on days 1-21, oral aspirin (or other deep vein thrombosis prophylaxis at the discretion of the principal investigator) once daily on days 1-28, and standard-dose oral dexamethasone once daily on days 1-4, 9-12, and 17-20. After 4 cycles of treatment, patients may discontinue treatment. For patients continuing therapy beyond 4 cycles, coumadin was discontinued and aspirin was given instead.
All-Cause Mortality
	Arm I (Lenalidomide, Dexamethasone) Step 1	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 1	Arm I (Lenalidomide, Dexamethasone) Step 2	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 2	Arm III (Expansion; Lenalidomide, Dexamethasone, Aspirin)	Arm IV (Expansion; Lenalidomide, Dexamethasone, Coumadin)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm I (Lenalidomide, Dexamethasone) Step 1	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 1	Arm I (Lenalidomide, Dexamethasone) Step 2	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 2	Arm III (Expansion; Lenalidomide, Dexamethasone, Aspirin)	Arm IV (Expansion; Lenalidomide, Dexamethasone, Coumadin)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	146/223 (65.47%)	112/220 (50.91%)	1/4 (25.00%)	3/14 (21.43%)	2/4 (50.00%)	1/3 (33.33%)
Blood and lymphatic system disorders
Thrombotic microangiopathy ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Febrile neutropenia ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cardiac disorders
Atrial fibrillation ^† 1	5/223 (2.24%)	0/220 (0.00%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Atrial flutter ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Supraventricular arrhythmia NOS ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Ventricular tachycardia ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cardiac-ischemia ^† 1	7/223 (3.14%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cardiac troponin T (cTnT) ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Left ventricular diastolic dysfunction ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Left ventricular systolic dysfunction ^† 1	3/223 (1.35%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cardiac/heart, pain ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Endocrine disorders
Adrenal insufficiency ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Endocrine-other ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Eye disorders
Nonneuropathic extraocular muscle weak ^† 1	11/223 (4.93%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cataract ^† 1	2/223 (0.90%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Vision-blurred ^† 1	3/223 (1.35%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Gastrointestinal disorders
Constipation ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Diarrhea w/o prior colostomy ^† 1	4/223 (1.79%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Esophagitis ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Fistula, Ileum ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Gastritis ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Dyspepsia ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Muco/stomatitis (symptom) oral cavity ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nausea ^† 1	3/223 (1.35%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Perforation, colon ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Ulcer, gastric ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Vomiting ^† 1	3/223 (1.35%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Gastrointestinal (GI) - other ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Duodenum, hemorrhage ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Rectum, hemorrhage ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Abdomen, pain ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
General disorders
Fatigue ^† 1	33/223 (14.80%)	21/220 (9.55%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	1/3 (33.33%)
Fever w/o neutropenia ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Rigors/chills ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Death - sudden death ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Edema head and neck ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Edema limb ^† 1	14/223 (6.28%)	3/220 (1.36%)	0/4 (0.00%)	1/14 (7.14%)	1/4 (25.00%)	0/3 (0.00%)
Edema trunk/genital ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Chest/thoracic pain NOS ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Pain - other ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infections and infestations
Infection w/ grade 3-4 neutropenia, colon ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 3-4 neutropenia, lung ^† 1	1/223 (0.45%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Infection with grade 3-4 neutropenia, upper airway ^† 1	0/223 (0.00%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 3-4 neutropenia, urinary tract ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Infection with grade 0-2 neutropenia, brain ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, bronchus ^† 1	0/223 (0.00%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, colon ^† 1	0/223 (0.00%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Infection with grade 0-2 neutropenia, esophagus ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, lip/perioral ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, lung ^† 1	11/223 (4.93%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, middle ear ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, skin ^† 1	6/223 (2.69%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, urinary tract ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Colon infection with unknown absolute neutrophil count (ANC) ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Lung infection with unknown absolute neutrophil count (ANC) ^† 1	1/223 (0.45%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Wound infection with unknown absolute neutrophil count (ANC) ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Opportunistic infection associated with >= Grade 1 lymphopenia ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 3-4 neutropenia, blood ^† 1	3/223 (1.35%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection with grade 0-2 neutropenia, blood ^† 1	3/223 (1.35%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection w/ unk ANC blood ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Infection - other ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Injury, poisoning and procedural complications
Fracture ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Vascular access,Thrombosis/embolism ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Investigations
Weight gain ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Weight loss ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Alkaline phosphatase increased ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Alanine aminotransferase (ALT) increased ^† 1	6/223 (2.69%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Aspartate aminotransferase (AST) increased ^† 1	3/223 (1.35%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Bilirubin increased ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Creatinine increased ^† 1	6/223 (2.69%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Lipase increased ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Metabolism and nutrition disorders
Pancreatic glucose intolerance ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Anorexia ^† 1	9/223 (4.04%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Dehydration ^† 1	9/223 (4.04%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Hypoalbuminemia ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypercalcemia ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypocalcemia ^† 1	16/223 (7.17%)	8/220 (3.64%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hyperglycemia ^† 1	25/223 (11.21%)	13/220 (5.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypoglycemia ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hyperkalemia ^† 1	2/223 (0.90%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypokalemia ^† 1	17/223 (7.62%)	8/220 (3.64%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hyponatremia ^† 1	12/223 (5.38%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Metabolic/Laboratory - other ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Urinary electrolyte wasting ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Musculoskeletal and connective tissue disorders
Arthritis ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Joint effusion ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nonneuropathic lower extr muscle weak ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nonneuropathic generalized weakness ^† 1	13/223 (5.83%)	4/220 (1.82%)	1/4 (25.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Back pain ^† 1	4/223 (1.79%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Bone pain ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Chest wall pain ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Extremity-limb, pain ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Joint pain ^† 1	1/223 (0.45%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Muscle pain ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nervous system disorders
Ataxia ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Central nervous system (CNS) cerebrovascular ischemia ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cognitive disturbance ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Dizziness ^† 1	6/223 (2.69%)	3/220 (1.36%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Encephalopathy ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Extrapyramidal movement ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Memory impairment ^† 1	3/223 (1.35%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Neuropathy cranial nerves (CN) II vision ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Neuropathy-motor ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Neuropathy-sensory ^† 1	2/223 (0.90%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Seizure ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Depressed level of consciousness ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Speech impairment ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Syncope ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Tremor ^† 1	4/223 (1.79%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Headache ^† 1	1/223 (0.45%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Neuropathic, pain ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Psychiatric disorders
Insomnia ^† 1	5/223 (2.24%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Confusion ^† 1	4/223 (1.79%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Agitation ^† 1	2/223 (0.90%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Anxiety ^† 1	1/223 (0.45%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Depression ^† 1	7/223 (3.14%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Psychosis ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Renal and urinary disorders
Renal failure ^† 1	4/223 (1.79%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Urinary retention ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Lung, hemorrhage ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nose, hemorrhage ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Adult Respiratory Distress Syndrome (ARDS) ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Cough ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Dyspnea ^† 1	14/223 (6.28%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	2/4 (50.00%)	0/3 (0.00%)
Hiccoughs ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypoxia ^† 1	3/223 (1.35%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Pleural effusion (non-malignant) ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Pneumonitis/pulmonary infiltrates ^† 1	8/223 (3.59%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Pulmonary/Upper Respiratory-other ^† 1	2/223 (0.90%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Skin and subcutaneous tissue disorders
Dry skin ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Pruritus/itching ^† 1	0/223 (0.00%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Rash/desquamation ^† 1	5/223 (2.24%)	9/220 (4.09%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Rash: acne/acneiform ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Erythema multiforme ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Vascular disorders
Vasculitis ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypertension ^† 1	2/223 (0.90%)	4/220 (1.82%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypotension ^† 1	2/223 (0.90%)	2/220 (0.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Hemorrhage-other ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Thrombosis/thrombus/embolism ^† 1	56/223 (25.11%)	28/220 (12.73%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Vascular-Other ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I (Lenalidomide, Dexamethasone) Step 1	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 1	Arm I (Lenalidomide, Dexamethasone) Step 2	Arm II (Lenalidomide, Low-dose Dexamethasone) Step 2	Arm III (Expansion; Lenalidomide, Dexamethasone, Aspirin)	Arm IV (Expansion; Lenalidomide, Dexamethasone, Coumadin)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	222/223 (99.55%)	216/220 (98.18%)	4/4 (100.00%)	14/14 (100.00%)	4/4 (100.00%)	3/3 (100.00%)
Eye disorders
Nonneuropathic extraocular muscle weak ^† 1	51/223 (22.87%)	27/220 (12.27%)	1/4 (25.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Vision - blurred ^† 1	39/223 (17.49%)	36/220 (16.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Gastrointestinal disorders
Constipation ^† 1	74/223 (33.18%)	87/220 (39.55%)	3/4 (75.00%)	8/14 (57.14%)	0/4 (0.00%)	1/3 (33.33%)
Diarrhea w/o prior colostomy ^† 1	36/223 (16.14%)	45/220 (20.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	2/3 (66.67%)
Dyspepsia ^† 1	23/223 (10.31%)	19/220 (8.64%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	1/3 (33.33%)
Nausea ^† 1	49/223 (21.97%)	45/220 (20.45%)	0/4 (0.00%)	1/14 (7.14%)	1/4 (25.00%)	2/3 (66.67%)
Vomiting ^† 1	13/223 (5.83%)	13/220 (5.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Muco/stomatitis by exam, oral cavity ^† 1	9/223 (4.04%)	8/220 (3.64%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Muco/stomatitis (symptom) oral cavity ^† 1	7/223 (3.14%)	9/220 (4.09%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Ulcer, gastric ^† 1	5/223 (2.24%)	8/220 (3.64%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
General disorders
Fatigue ^† 1	132/223 (59.19%)	136/220 (61.82%)	2/4 (50.00%)	10/14 (71.43%)	3/4 (75.00%)	1/3 (33.33%)
Fever w/o neutropenia ^† 1	23/223 (10.31%)	12/220 (5.45%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Edema, limb ^† 1	90/223 (40.36%)	69/220 (31.36%)	2/4 (50.00%)	4/14 (28.57%)	1/4 (25.00%)	1/3 (33.33%)
Abdomen, pain ^† 1	10/223 (4.48%)	6/220 (2.73%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Pain NOS ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Infections and infestations
Infection with grade 0-2 neutropenia, bladder ^† 1	0/223 (0.00%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Opportunistic infection associated with >= Grade 1 lymphopenia ^† 1	0/223 (0.00%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Injury, poisoning and procedural complications
Bruising ^† 1	2/223 (0.90%)	7/220 (3.18%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Investigations
Weight gain ^† 1	30/223 (13.45%)	17/220 (7.73%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Weight loss ^† 1	18/223 (8.07%)	13/220 (5.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Alkaline phosphatase increased ^† 1	56/223 (25.11%)	50/220 (22.73%)	0/4 (0.00%)	2/14 (14.29%)	0/4 (0.00%)	0/3 (0.00%)
ALT increased ^† 1	78/223 (34.98%)	67/220 (30.45%)	0/4 (0.00%)	0/14 (0.00%)	2/4 (50.00%)	0/3 (0.00%)
AST increased ^† 1	50/223 (22.42%)	51/220 (23.18%)	1/4 (25.00%)	1/14 (7.14%)	3/4 (75.00%)	0/3 (0.00%)
Bilirubin increased ^† 1	24/223 (10.76%)	24/220 (10.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Creatinine increased ^† 1	57/223 (25.56%)	58/220 (26.36%)	0/4 (0.00%)	2/14 (14.29%)	0/4 (0.00%)	2/3 (66.67%)
Metabolism and nutrition disorders
Anorexia ^† 1	28/223 (12.56%)	18/220 (8.18%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypercalcemia ^† 1	3/223 (1.35%)	13/220 (5.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Hypocalcemia ^† 1	130/223 (58.30%)	114/220 (51.82%)	0/4 (0.00%)	3/14 (21.43%)	3/4 (75.00%)	2/3 (66.67%)
Hyperglycemia ^† 1	153/223 (68.61%)	151/220 (68.64%)	2/4 (50.00%)	7/14 (50.00%)	2/4 (50.00%)	1/3 (33.33%)
Hypoglycemia ^† 1	18/223 (8.07%)	10/220 (4.55%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hyperkalemia ^† 1	17/223 (7.62%)	16/220 (7.27%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hypokalemia ^† 1	68/223 (30.49%)	67/220 (30.45%)	0/4 (0.00%)	1/14 (7.14%)	1/4 (25.00%)	2/3 (66.67%)
Hypernatremia ^† 1	13/223 (5.83%)	22/220 (10.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Hyponatremia ^† 1	76/223 (34.08%)	59/220 (26.82%)	0/4 (0.00%)	1/14 (7.14%)	2/4 (50.00%)	1/3 (33.33%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	26/223 (11.66%)	22/220 (10.00%)	1/4 (25.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Extremity-limb, pain ^† 1	13/223 (5.83%)	11/220 (5.00%)	0/4 (0.00%)	2/14 (14.29%)	0/4 (0.00%)	0/3 (0.00%)
Muscle pain ^† 1	14/223 (6.28%)	18/220 (8.18%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Nonneuropathic generalized weakness ^† 1	6/223 (2.69%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Nervous system disorders
Taste disturbance ^† 1	20/223 (8.97%)	17/220 (7.73%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Dizziness ^† 1	45/223 (20.18%)	25/220 (11.36%)	1/4 (25.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Neuropathy-sensory ^† 1	83/223 (37.22%)	68/220 (30.91%)	1/4 (25.00%)	4/14 (28.57%)	0/4 (0.00%)	0/3 (0.00%)
Tremor ^† 1	45/223 (20.18%)	37/220 (16.82%)	2/4 (50.00%)	2/14 (14.29%)	0/4 (0.00%)	0/3 (0.00%)
Headache ^† 1	21/223 (9.42%)	18/220 (8.18%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Ataxia ^† 1	4/223 (1.79%)	1/220 (0.45%)	0/4 (0.00%)	2/14 (14.29%)	0/4 (0.00%)	0/3 (0.00%)
Depressed level of consciousness ^† 1	5/223 (2.24%)	7/220 (3.18%)	0/4 (0.00%)	3/14 (21.43%)	0/4 (0.00%)	0/3 (0.00%)
Psychiatric disorders
Insomnia ^† 1	76/223 (34.08%)	84/220 (38.18%)	0/4 (0.00%)	2/14 (14.29%)	2/4 (50.00%)	1/3 (33.33%)
Anxiety ^† 1	19/223 (8.52%)	5/220 (2.27%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Depression ^† 1	54/223 (24.22%)	42/220 (19.09%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Confusion ^† 1	11/223 (4.93%)	8/220 (3.64%)	1/4 (25.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Renal and urinary disorders
Urinary retention ^† 1	0/223 (0.00%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	10/223 (4.48%)	7/220 (3.18%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Dyspnea ^† 1	40/223 (17.94%)	38/220 (17.27%)	1/4 (25.00%)	2/14 (14.29%)	0/4 (0.00%)	0/3 (0.00%)
Nasal cavity/paranasal sinus reaction ^† 1	0/223 (0.00%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Allergic rhinitis ^† 1	1/223 (0.45%)	3/220 (1.36%)	0/4 (0.00%)	1/14 (7.14%)	0/4 (0.00%)	0/3 (0.00%)
Skin and subcutaneous tissue disorders
Sweating ^† 1	21/223 (9.42%)	18/220 (8.18%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Dry skin ^† 1	7/223 (3.14%)	3/220 (1.36%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	1/3 (33.33%)
Pruritus/itching ^† 1	15/223 (6.73%)	32/220 (14.55%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
Rash/desquamation ^† 1	36/223 (16.14%)	60/220 (27.27%)	0/4 (0.00%)	1/14 (7.14%)	1/4 (25.00%)	1/3 (33.33%)
Hand-foot reaction ^† 1	1/223 (0.45%)	0/220 (0.00%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Petechiae ^† 1	1/223 (0.45%)	1/220 (0.45%)	0/4 (0.00%)	0/14 (0.00%)	1/4 (25.00%)	0/3 (0.00%)
Vascular disorders
Flushing ^† 1	8/223 (3.59%)	13/220 (5.91%)	0/4 (0.00%)	0/14 (0.00%)	0/4 (0.00%)	0/3 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, CTCAE (3.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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

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Name/Title:	Study Statistician
Organization:	ECOG Statistical Office
Phone:	617-632-3012

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baker A, Braggio E, Jacobus S, Jung S, Larson D, Therneau T, Dispenzieri A, Van Wier SA, Ahmann G, Levy J, Perkins L, Kim S, Henderson K, Vesole D, Rajkumar SV, Jelinek DF, Carpten J, Fonseca R. Uncovering the biology of multiple myeloma among African Americans: a comprehensive genomics approach. Blood. 2013 Apr 18;121(16):3147-52. doi: 10.1182/blood-2012-07-443606. Epub 2013 Feb 19.

Kumar SK, Uno H, Jacobus SJ, Van Wier SA, Ahmann GJ, Henderson KJ, Callander NS, Haug JL, Siegel DS, Greipp PR, Fonseca R, Rajkumar SV. Impact of gene expression profiling-based risk stratification in patients with myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood. 2011 Oct 20;118(16):4359-62. doi: 10.1182/blood-2011-03-342089. Epub 2011 Aug 22.

Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, Abonour R, Siegel DS, Katz M, Greipp PR; Eastern Cooperative Oncology Group. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan;11(1):29-37. doi: 10.1016/S1470-2045(09)70284-0. Epub 2009 Oct 21. Erratum In: Lancet Oncol. 2010 Jan;11(1):14.

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Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00098475
Other Study ID Numbers:	NCI-2012-03150 NCI-2012-03150 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) E4A03 CDR0000404161 E4A03 ( Other Identifier: ECOG-ACRIN Cancer Research Group ) E4A03 ( Other Identifier: CTEP ) U10CA180820 ( U.S. NIH Grant/Contract ) U10CA021115 ( U.S. NIH Grant/Contract )
First Submitted:	December 7, 2004
First Posted:	December 8, 2004
Results First Submitted:	August 30, 2013
Results First Posted:	January 22, 2014
Last Update Posted:	May 16, 2024

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