Lenalidomide and Dexamethasone With or Without Bortezomib in Treating Patients With Previously Untreated Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT00644228

Recruitment Status : Active, not recruiting

First Posted : March 26, 2008

Results First Posted : July 6, 2017

Last Update Posted : April 4, 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: None (Open Label); Primary Purpose: Treatment
Conditions	DS Stage I Multiple Myeloma DS Stage II Multiple Myeloma DS Stage III Multiple Myeloma
Interventions	Drug: Bortezomib Drug: Dexamethasone Other: Laboratory Biomarker Analysis Drug: Lenalidomide
Enrollment	525

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Period Title: Randomization & Eligibility
Started	261	264
Eligible and Analyzable ^[1]	229	242
Completed ^[2]	229	242
Not Completed	32	22
Reason Not Completed
Ineligible	31	21
Withdrew Consent prior to therapy start	1	0
Invalid Consent	0	1
[1] All patients who were consented and did not withdraw consent prior to treatment are "Analyzable". [2] "Completed" does not apply to this study period.
Period Title: Induction Therapy
Started	229	242
Completed	146	137
Not Completed	83	105
Reason Not Completed
Adverse Event	22	55
Withdrawal by Subject	10	3
Progression/Relapse	24	12
Death	3	7
Not Protocol-Specified	24	28
Period Title: Maintenance
Started	143 ^[1]	135 ^[2]
Completed ^[3]	0	0
Not Completed	143	135
Reason Not Completed
Adverse Event	27	31
Withdrawal by Subject	6	4
Progression/Relapse	67	42
Death	3	3
Not Protocol-Specified	14	15
On Treatment	26	40
[1] 3 patients who completed induction did not continue on to maintenance due to refusal (1), other (2). [2] 2 patients who completed induction did not continue on to maintenance due to other (2). [3] Patients were treated until progression or removal/refusal. "Completed" does not apply.

Baseline Characteristics

Arm/Group Title		Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)	Total
Arm/Group Description		Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...	Total of all reporting groups
Arm/Group Description		Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Total of all reporting groups
Overall Number of Baseline Participants		229	242	471
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Includes all eligible and analyzable patients.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	229 participants	242 participants	471 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	120 52.4%	149 61.6%	269 57.1%
	>=65 years	109 47.6%	93 38.4%	202 42.9%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	229 participants	242 participants	471 participants
	Female	107 46.7%	89 36.8%	196 41.6%
	Male	122 53.3%	153 63.2%	275 58.4%
ISS Stage ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	229 participants	242 participants	471 participants
	ISS Stage I or II	150 65.5%	164 67.8%	314 66.7%
	ISS Stage III	79 34.5%	78 32.2%	157 33.3%
		[1] Measure Description: International Staging System (ISS) Criteria: Stage I: Serum β2-microglobulin < 3.5mg/L and Serum Albumin ≥ 3.5 g/dL; expected median survival is 62 months. Stage II: Not Stage I or III; expected median survival is 44 months. Stage III: Serum β2-microglobulin > 5.5 mg/L; expected median survival is 29 months. There are two categories for stage II: serum β2-microglobulin < 3.5 mg/L but serum albumin < 3.5 g/dL; or serum β2-microglobulin 3.5 to < 5.5 mg/L irrespective of the serum albumin level.

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival
Description	Unstratified median progression-free survival in months.
Description	Unstratified median progression-free survival in months.
Time Frame	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients are included. An analyzable patient is one who provided valid consent and who did not withdraw consent prior to initiating treatment.


Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description:	Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...
Arm/Group Description:	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Overall Number of Participants Analyzed	229	242
Median (95% Confidence Interval) Unit of Measure: Months
	30 (29 to 39)	43 (39 to 52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments	With four years of patient accrual and two and a half years of follow-up, 220 patients per arm yields 87% power to detect an increase of PFS of 50%, from a median of 3 years to 4.5 years, which corresponds to a hazard ratio of 1.5. These calculations are based on a one-sided stratified log-rank test at level 0.025 with two interim analyses. The final analysis will be carried out at the 0.02 significance level to allow for two interim analyses at the 0.0025 significance level.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0018
	Comments	The p-value is from a one-sided, stratified log-rank test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.712
	Confidence Interval	(2-Sided) 96% 0.560 to 0.906
	Estimation Comments	The hazard ratio compares Bortezomib/Lenalidomide/Dexamethasone against Lenalidomide/Dexamethasone.

2.Secondary Outcome


Title	Overall Survival
Description	Unstratified median overall survival in months.
Description	Unstratified median overall survival in months.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients are included. An analyzable patient is one who provided valid consent and who did not withdraw consent prior to initiating treatment.


Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description:	Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...
Arm/Group Description:	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Overall Number of Participants Analyzed	229	242
Median (95% Confidence Interval) Unit of Measure: Months
	64 ^[1] (56 to NA)	75 ^[1] (65 to NA)

[1]

The upper bound of the confidence interval has not yet been reached.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments	Overall survival will be compared between the two treatment arms using a stratified log-rank test.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0250
	Comments	The p-value is based on a two-sided, stratified log rank test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Log Rank
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.709
	Confidence Interval	(2-Sided) 95% 0.524 to 0.959
	Estimation Comments	The hazard ratio compares Bortezomib/Lenalidomide/Dexamethasone against Lenalidomide/Dexamethasone.

3.Secondary Outcome


Title	Response Rates ()
Description	The response rate was calculated as the number of patients with docume...
Description	The response rate was calculated as the number of patients with documented confirmed partial response (PR) or better, which includes confirmed/unconfirmed stringent complete response (sCR), confirmed/unconfirmed complete response (CR), confirmed/unconfirmed very good partial response (VGPR), or confirmed partial response (PR), as best response divided by the total number of evaluable patients, in each arm. Patients with measurable disease, as defined in the protocol, are evaluable. Response rates were compared between the two treatment arms using a stratified Cochran-Mantel-Haenszel test. Response designations were based on the International Uniform Response Criteria for Multiple Myeloma. Due to the complexity of these criteria, the details of these criteria have been omitted.
Time Frame	Up to 6 years

Outcome Measure Data

Analysis Population Description

All eligible, analyzable patients are included.


Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description:	Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...
Arm/Group Description:	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
Overall Number of Participants Analyzed	229	242
Measure Type: Count of Participants Unit of Measure: Participants
	153 66.8%	176 72.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Dexamethasone and Lenalidomide), Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.20
	Comments	The p-value is based on a stratified Cochran-Mantel-Haenszel test. Stratification factors include those factors by which patients were randomized: intent to transplant (yes vs no) and ISS Stage (I vs II vs III).
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The number at risk excludes patients who went off study prior to starting treatment and were thus not evaluated for toxicity. The adverse events reported here are current up through the time of upload of these data.

Arm/Group Title	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
Arm/Group Description	Patients receive dexamethasone PO Q...	Patients receive dexamethasone PO Q...
Arm/Group Description	Patients receive dexamethasone PO QD on days 1, 8, 15, and 22 and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO	Patients receive dexamethasone PO QD on days 1, 2, 4, 5, 8, 9, 11, and 12; lenalidomide PO QD on days 1-14; and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Bortezomib: Given IV Dexamethasone: Given PO Laboratory Biomarker Analysis: Optional correlative studies Lenalidomide: Given PO
All-Cause Mortality
	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Arm I (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	105/222 (47.30%)	124/237 (52.32%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1	5/222 (2.25%)	0/237 (0.00%)
Hemoglobin ^† 1	24/222 (10.81%)	13/237 (5.49%)
Hemolysis ^† 1	1/222 (0.45%)	0/237 (0.00%)
Cardiac disorders
Cardiac Arrhythmia-Other ^† 1	0/222 (0.00%)	1/237 (0.42%)
Cardiac General-Other ^† 1	1/222 (0.45%)	3/237 (1.27%)
Cardiac-ischemia/infarction ^† 1	4/222 (1.80%)	1/237 (0.42%)
Conduction abnormality NOS ^† 1	1/222 (0.45%)	1/237 (0.42%)
Left ventricular diastolic dysfunction ^† 1	4/222 (1.80%)	1/237 (0.42%)
Left ventricular systolic dysfunction ^† 1	4/222 (1.80%)	0/237 (0.00%)
Pain - Cardiac/heart ^† 1	2/222 (0.90%)	0/237 (0.00%)
SVT and nodal arrhythmia - Atrial fibrillation ^† 1	5/222 (2.25%)	5/237 (2.11%)
SVT and nodal arrhythmia - Atrial flutter ^† 1	1/222 (0.45%)	0/237 (0.00%)
SVT and nodal arrhythmia - Sinus bradycardia ^† 1	1/222 (0.45%)	2/237 (0.84%)
SVT and nodal arrhythmia - Sinus tachycardia ^† 1	1/222 (0.45%)	0/237 (0.00%)
Valvular heart disease ^† 1	1/222 (0.45%)	0/237 (0.00%)
Endocrine disorders
Thyroid function, high ^† 1	0/222 (0.00%)	1/237 (0.42%)
Eye disorders
Cataract ^† 1	1/222 (0.45%)	0/237 (0.00%)
Dry eye syndrome ^† 1	0/222 (0.00%)	1/237 (0.42%)
Ocular/Visual-Other ^† 1	0/222 (0.00%)	1/237 (0.42%)
Ophthalmoplegia/diplopia (double vision) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Vision-blurred vision ^† 1	0/222 (0.00%)	1/237 (0.42%)
Gastrointestinal disorders
Colitis ^† 1	0/222 (0.00%)	2/237 (0.84%)
Constipation ^† 1	0/222 (0.00%)	2/237 (0.84%)
Diarrhea ^† 1	6/222 (2.70%)	10/237 (4.22%)
Dry mouth/salivary gland (xerostomia) ^† 1	1/222 (0.45%)	1/237 (0.42%)
Dysphagia (difficulty swallowing) ^† 1	1/222 (0.45%)	1/237 (0.42%)
Gastritis (including bile reflux gastritis) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Gastrointestinal-Other ^† 1	0/222 (0.00%)	2/237 (0.84%)
Hemorrhage, GI - Lower GI NOS ^† 1	1/222 (0.45%)	4/237 (1.69%)
Hemorrhage, GI - Rectum ^† 1	2/222 (0.90%)	1/237 (0.42%)
Hemorrhage, GI - Stomach ^† 1	0/222 (0.00%)	1/237 (0.42%)
Hemorrhage, GI - Upper GI NOS ^† 1	0/222 (0.00%)	1/237 (0.42%)
Hemorrhage, GI - Varices (rectal) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Ileus, GI (functional obstruction of bowel) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Nausea ^† 1	2/222 (0.90%)	2/237 (0.84%)
Obstruction, GI - Colon ^† 1	1/222 (0.45%)	0/237 (0.00%)
Obstruction, GI - Small bowel NOS ^† 1	0/222 (0.00%)	3/237 (1.27%)
Obstruction, GI - Stomach ^† 1	0/222 (0.00%)	1/237 (0.42%)
Pain - Abdomen NOS ^† 1	2/222 (0.90%)	5/237 (2.11%)
Perforation, GI - Colon ^† 1	1/222 (0.45%)	1/237 (0.42%)
Typhlitis (cecal inflammation) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Vomiting ^† 1	1/222 (0.45%)	3/237 (1.27%)
General disorders
Death - Multi-organ failure ^† 1	0/222 (0.00%)	1/237 (0.42%)
Death not associated with CTCAE term - Death NOS ^† 1	1/222 (0.45%)	4/237 (1.69%)
Edema: limb ^† 1	1/222 (0.45%)	2/237 (0.84%)
Extremity-lower (gait/walking) ^† 1	1/222 (0.45%)	1/237 (0.42%)
Fatigue (asthenia, lethargy, malaise) ^† 1	5/222 (2.25%)	8/237 (3.38%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L ^† 1	1/222 (0.45%)	0/237 (0.00%)
Flu-like syndrome ^† 1	0/222 (0.00%)	2/237 (0.84%)
Pain - Chest/thorax NOS ^† 1	0/222 (0.00%)	3/237 (1.27%)
Pain - Pain NOS ^† 1	1/222 (0.45%)	3/237 (1.27%)
Pain-Other ^† 1	0/222 (0.00%)	1/237 (0.42%)
Sudden death ^† 1	1/222 (0.45%)	1/237 (0.42%)
Hepatobiliary disorders
Cholecystitis ^† 1	0/222 (0.00%)	2/237 (0.84%)
Hepatobiliary/Pancreas-Other ^† 1	1/222 (0.45%)	0/237 (0.00%)
Liver dysfunction/failure (clinical) ^† 1	2/222 (0.90%)	2/237 (0.84%)
Pain - Gallbladder ^† 1	1/222 (0.45%)	0/237 (0.00%)
Immune system disorders
Allergic reaction/hypersensitivity ^† 1	1/222 (0.45%)	1/237 (0.42%)
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile) ^† 1	1/222 (0.45%)	2/237 (0.84%)
Inf (clin/microbio) w/Gr 3-4 neuts - Blood ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf (clin/microbio) w/Gr 3-4 neuts - Cecum ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf (clin/microbio) w/Gr 3-4 neuts - Lung ^† 1	3/222 (1.35%)	3/237 (1.27%)
Inf (clin/microbio) w/Gr 3-4 neuts - UTI ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood ^† 1	0/222 (0.00%)	2/237 (0.84%)
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter ^† 1	0/222 (0.00%)	1/237 (0.42%)
Inf w/normal ANC or Gr 1-2 neutrophils - Colon ^† 1	1/222 (0.45%)	0/237 (0.00%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung ^† 1	6/222 (2.70%)	8/237 (3.38%)
Inf w/normal ANC or Gr 1-2 neutrophils - UTI ^† 1	1/222 (0.45%)	5/237 (2.11%)
Inf w/normal ANC or Gr 1-2 neutrophils - Wound ^† 1	2/222 (0.90%)	0/237 (0.00%)
Infection with unknown ANC - Anal/perianal ^† 1	0/222 (0.00%)	1/237 (0.42%)
Infection with unknown ANC - Blood ^† 1	3/222 (1.35%)	4/237 (1.69%)
Infection with unknown ANC - Bone (osteomyelitis) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Infection with unknown ANC - Bronchus ^† 1	0/222 (0.00%)	1/237 (0.42%)
Infection with unknown ANC - Catheter-related ^† 1	0/222 (0.00%)	1/237 (0.42%)
Infection with unknown ANC - Eye NOS ^† 1	1/222 (0.45%)	0/237 (0.00%)
Infection with unknown ANC - Heart (endocarditis) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Infection with unknown ANC - Joint ^† 1	1/222 (0.45%)	1/237 (0.42%)
Infection with unknown ANC - Lung (pneumonia) ^† 1	15/222 (6.76%)	10/237 (4.22%)
Infection with unknown ANC - Meninges (meningitis) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Infection with unknown ANC - Mucosa ^† 1	0/222 (0.00%)	1/237 (0.42%)
Infection with unknown ANC - Pharynx ^† 1	1/222 (0.45%)	0/237 (0.00%)
Infection with unknown ANC - Sinus ^† 1	1/222 (0.45%)	0/237 (0.00%)
Infection with unknown ANC - Skin (cellulitis) ^† 1	0/222 (0.00%)	4/237 (1.69%)
Infection with unknown ANC - Upper airway NOS ^† 1	0/222 (0.00%)	2/237 (0.84%)
Infection with unknown ANC - Urinary tract NOS ^† 1	2/222 (0.90%)	2/237 (0.84%)
Infection-Other ^† 1	5/222 (2.25%)	4/237 (1.69%)
Injury, poisoning and procedural complications
Fracture ^† 1	4/222 (1.80%)	6/237 (2.53%)
Thrombosis/embolism (vascular access-related) ^† 1	1/222 (0.45%)	3/237 (1.27%)
Wound complication, non-infectious ^† 1	0/222 (0.00%)	1/237 (0.42%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) ^† 1	2/222 (0.90%)	3/237 (1.27%)
AST, SGOT ^† 1	2/222 (0.90%)	1/237 (0.42%)
Alkaline phosphatase ^† 1	1/222 (0.45%)	1/237 (0.42%)
Bilirubin (hyperbilirubinemia) ^† 1	1/222 (0.45%)	1/237 (0.42%)
Cardiac troponin I (cTnI) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Creatinine ^† 1	9/222 (4.05%)	7/237 (2.95%)
INR (of prothrombin time) ^† 1	1/222 (0.45%)	3/237 (1.27%)
Leukocytes (total WBC) ^† 1	2/222 (0.90%)	3/237 (1.27%)
Lymphopenia ^† 1	0/222 (0.00%)	5/237 (2.11%)
Metabolic/Laboratory-Other ^† 1	0/222 (0.00%)	1/237 (0.42%)
Neutrophils/granulocytes (ANC/AGC) ^† 1	2/222 (0.90%)	5/237 (2.11%)
PTT (Partial thromboplastin time) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Platelets ^† 1	5/222 (2.25%)	13/237 (5.49%)
Weight loss ^† 1	1/222 (0.45%)	2/237 (0.84%)
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Albumin, serum-low (hypoalbuminemia) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Anorexia ^† 1	2/222 (0.90%)	5/237 (2.11%)
Calcium, serum-high (hypercalcemia) ^† 1	2/222 (0.90%)	2/237 (0.84%)
Calcium, serum-low (hypocalcemia) ^† 1	6/222 (2.70%)	5/237 (2.11%)
Dehydration ^† 1	9/222 (4.05%)	17/237 (7.17%)
Glucose, serum-high (hyperglycemia) ^† 1	6/222 (2.70%)	6/237 (2.53%)
Glucose, serum-low (hypoglycemia) ^† 1	2/222 (0.90%)	1/237 (0.42%)
Phosphate, serum-low (hypophosphatemia) ^† 1	1/222 (0.45%)	2/237 (0.84%)
Potassium, serum-low (hypokalemia) ^† 1	2/222 (0.90%)	12/237 (5.06%)
Sodium, serum-high (hypernatremia) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Sodium, serum-low (hyponatremia) ^† 1	3/222 (1.35%)	5/237 (2.11%)
Tumor lysis syndrome ^† 1	2/222 (0.90%)	2/237 (0.84%)
Uric acid, serum-high (hyperuricemia) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Musculoskeletal and connective tissue disorders
Arthritis (non-septic) ^† 1	1/222 (0.45%)	2/237 (0.84%)
Joint-effusion ^† 1	0/222 (0.00%)	1/237 (0.42%)
Muscle weakness, not d/t neuropathy - Extrem-lower ^† 1	1/222 (0.45%)	4/237 (1.69%)
Muscle weakness, not d/t neuropathy - body/general ^† 1	3/222 (1.35%)	11/237 (4.64%)
Musculoskeletal/Soft Tissue-Other ^† 1	1/222 (0.45%)	3/237 (1.27%)
Osteonecrosis (avascular necrosis) ^† 1	2/222 (0.90%)	1/237 (0.42%)
Pain - Back ^† 1	4/222 (1.80%)	4/237 (1.69%)
Pain - Bone ^† 1	3/222 (1.35%)	1/237 (0.42%)
Pain - Chest wall ^† 1	1/222 (0.45%)	0/237 (0.00%)
Pain - Extremity-limb ^† 1	1/222 (0.45%)	2/237 (0.84%)
Pain - Joint ^† 1	1/222 (0.45%)	1/237 (0.42%)
Pain - Muscle ^† 1	1/222 (0.45%)	0/237 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death - Disease progression NOS ^† 1	2/222 (0.90%)	0/237 (0.00%)
Myelodysplasia ^† 1	1/222 (0.45%)	0/237 (0.00%)
Secondary Malignancy-poss rel to cancer Tx ^† 1	3/222 (1.35%)	2/237 (0.84%)
Nervous system disorders
CNS cerebrovascular ischemia ^† 1	3/222 (1.35%)	1/237 (0.42%)
Cognitive disturbance ^† 1	2/222 (0.90%)	0/237 (0.00%)
Dizziness ^† 1	0/222 (0.00%)	4/237 (1.69%)
Encephalopathy ^† 1	3/222 (1.35%)	1/237 (0.42%)
Hemorrhage, CNS ^† 1	1/222 (0.45%)	0/237 (0.00%)
Neurology-Other ^† 1	3/222 (1.35%)	1/237 (0.42%)
Neuropathy: motor ^† 1	1/222 (0.45%)	2/237 (0.84%)
Neuropathy: sensory ^† 1	2/222 (0.90%)	7/237 (2.95%)
Ocular/Visual-Other ^† 1	0/222 (0.00%)	1/237 (0.42%)
Pain - Head/headache ^† 1	0/222 (0.00%)	1/237 (0.42%)
Seizure ^† 1	0/222 (0.00%)	2/237 (0.84%)
Somnolence/depressed level of consciousness ^† 1	3/222 (1.35%)	2/237 (0.84%)
Syncope (fainting) ^† 1	5/222 (2.25%)	12/237 (5.06%)
Taste alteration (dysgeusia) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Tremor ^† 1	0/222 (0.00%)	2/237 (0.84%)
Psychiatric disorders
Confusion ^† 1	5/222 (2.25%)	3/237 (1.27%)
Mood alteration - depression ^† 1	0/222 (0.00%)	1/237 (0.42%)
Psychosis (hallucinations/delusions) ^† 1	1/222 (0.45%)	0/237 (0.00%)
Renal and urinary disorders
Fistula, GU - Bladder ^† 1	0/222 (0.00%)	1/237 (0.42%)
Glomerular filtration rate ^† 1	1/222 (0.45%)	1/237 (0.42%)
Hemorrhage, GU - Urinary NOS ^† 1	1/222 (0.45%)	0/237 (0.00%)
Incontinence, urinary ^† 1	1/222 (0.45%)	0/237 (0.00%)
Renal failure ^† 1	13/222 (5.86%)	3/237 (1.27%)
Renal/Genitourinary-Other ^† 1	2/222 (0.90%)	2/237 (0.84%)
Urinary retention (including neurogenic bladder) ^† 1	1/222 (0.45%)	1/237 (0.42%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS) ^† 1	0/222 (0.00%)	2/237 (0.84%)
Bronchospasm, wheezing ^† 1	1/222 (0.45%)	0/237 (0.00%)
Cough ^† 1	1/222 (0.45%)	1/237 (0.42%)
Dyspnea (shortness of breath) ^† 1	4/222 (1.80%)	9/237 (3.80%)
Hypoxia ^† 1	4/222 (1.80%)	6/237 (2.53%)
Mucositis/stomatitis (clinical exam) - Pharynx ^† 1	1/222 (0.45%)	0/237 (0.00%)
Pain - Pleura ^† 1	0/222 (0.00%)	1/237 (0.42%)
Pleural effusion (non-malignant) ^† 1	2/222 (0.90%)	0/237 (0.00%)
Pneumonitis/pulmonary infiltrates ^† 1	3/222 (1.35%)	6/237 (2.53%)
Pulmonary/Upper Respiratory-Other ^† 1	4/222 (1.80%)	2/237 (0.84%)
Skin and subcutaneous tissue disorders
Rash/desquamation ^† 1	2/222 (0.90%)	1/237 (0.42%)
Skin breakdown/decubitus ulcer ^† 1	1/222 (0.45%)	0/237 (0.00%)
Urticaria (hives, welts, wheals) ^† 1	0/222 (0.00%)	1/237 (0.42%)
Vascular disorders
Hypertension ^† 1	2/222 (0.90%)	4/237 (1.69%)
Hypotension ^† 1	2/222 (0.90%)	16/237 (6.75%)
Thrombosis/thrombus/embolism ^† 1	9/222 (4.05%)	8/237 (3.38%)
† 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 (Dexamethasone and Lenalidomide)	Arm II (Dexamethasone, Lenalidomide, Bortezomib)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	209/222 (94.14%)	232/237 (97.89%)
Blood and lymphatic system disorders
Hemoglobin ^† 1	162/222 (72.97%)	172/237 (72.57%)
Ear and labyrinth disorders
Tinnitus ^† 1	19/222 (8.56%)	9/237 (3.80%)
Eye disorders
Cataract ^† 1	14/222 (6.31%)	19/237 (8.02%)
Dry eye syndrome ^† 1	13/222 (5.86%)	19/237 (8.02%)
Vision-blurred vision ^† 1	41/222 (18.47%)	53/237 (22.36%)
Gastrointestinal disorders
Constipation ^† 1	119/222 (53.60%)	141/237 (59.49%)
Diarrhea ^† 1	99/222 (44.59%)	113/237 (47.68%)
Distention/bloating, abdominal ^† 1	8/222 (3.60%)	13/237 (5.49%)
Dry mouth/salivary gland (xerostomia) ^† 1	27/222 (12.16%)	30/237 (12.66%)
Flatulence ^† 1	24/222 (10.81%)	22/237 (9.28%)
Gastrointestinal-Other ^† 1	12/222 (5.41%)	10/237 (4.22%)
Heartburn/dyspepsia ^† 1	43/222 (19.37%)	58/237 (24.47%)
Mucositis/stomatitis (clinical exam) - Oral cavity ^† 1	20/222 (9.01%)	16/237 (6.75%)
Mucositis/stomatitis (functional/symp) - Oral cav ^† 1	11/222 (4.95%)	17/237 (7.17%)
Nausea ^† 1	88/222 (39.64%)	105/237 (44.30%)
Pain - Abdomen NOS ^† 1	33/222 (14.86%)	43/237 (18.14%)
Pain - Dental/teeth/peridontal ^† 1	13/222 (5.86%)	6/237 (2.53%)
Vomiting ^† 1	38/222 (17.12%)	47/237 (19.83%)
General disorders
Edema: limb ^† 1	90/222 (40.54%)	114/237 (48.10%)
Extremity-lower (gait/walking) ^† 1	15/222 (6.76%)	15/237 (6.33%)
Fatigue (asthenia, lethargy, malaise) ^† 1	178/222 (80.18%)	191/237 (80.59%)
Fever in absence of neutropenia, ANC lt1.0x10e9/L ^† 1	37/222 (16.67%)	48/237 (20.25%)
Pain - Chest/thorax NOS ^† 1	11/222 (4.95%)	15/237 (6.33%)
Pain-Other ^† 1	36/222 (16.22%)	43/237 (18.14%)
Rigors/chills ^† 1	28/222 (12.61%)	34/237 (14.35%)
Infections and infestations
Inf w/normal ANC or Gr 1-2 neutrophils - Lung ^† 1	21/222 (9.46%)	20/237 (8.44%)
Inf w/normal ANC or Gr 1-2 neutrophils - Skin ^† 1	15/222 (6.76%)	11/237 (4.64%)
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway ^† 1	17/222 (7.66%)	20/237 (8.44%)
Infection-Other ^† 1	13/222 (5.86%)	29/237 (12.24%)
Injury, poisoning and procedural complications
Bruising (in absence of Gr 3-4 thrombocytopenia) ^† 1	23/222 (10.36%)	24/237 (10.13%)
Fracture ^† 1	8/222 (3.60%)	15/237 (6.33%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase) ^† 1	59/222 (26.58%)	70/237 (29.54%)
AST, SGOT ^† 1	50/222 (22.52%)	71/237 (29.96%)
Alkaline phosphatase ^† 1	50/222 (22.52%)	68/237 (28.69%)
Bilirubin (hyperbilirubinemia) ^† 1	23/222 (10.36%)	34/237 (14.35%)
Creatinine ^† 1	78/222 (35.14%)	69/237 (29.11%)
Leukocytes (total WBC) ^† 1	137/222 (61.71%)	124/237 (52.32%)
Lymphopenia ^† 1	72/222 (32.43%)	76/237 (32.07%)
Metabolic/Laboratory-Other ^† 1	20/222 (9.01%)	24/237 (10.13%)
Neutrophils/granulocytes (ANC/AGC) ^† 1	117/222 (52.70%)	91/237 (38.40%)
Platelets ^† 1	130/222 (58.56%)	144/237 (60.76%)
Weight gain ^† 1	22/222 (9.91%)	17/237 (7.17%)
Weight loss ^† 1	59/222 (26.58%)	62/237 (26.16%)
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia) ^† 1	79/222 (35.59%)	86/237 (36.29%)
Anorexia ^† 1	77/222 (34.68%)	92/237 (38.82%)
Calcium, serum-high (hypercalcemia) ^† 1	28/222 (12.61%)	17/237 (7.17%)
Calcium, serum-low (hypocalcemia) ^† 1	122/222 (54.95%)	130/237 (54.85%)
Dehydration ^† 1	19/222 (8.56%)	26/237 (10.97%)
Glucose, serum-high (hyperglycemia) ^† 1	140/222 (63.06%)	138/237 (58.23%)
Glucose, serum-low (hypoglycemia) ^† 1	25/222 (11.26%)	40/237 (16.88%)
Magnesium, serum-low (hypomagnesemia) ^† 1	30/222 (13.51%)	32/237 (13.50%)
Phosphate, serum-low (hypophosphatemia) ^† 1	33/222 (14.86%)	24/237 (10.13%)
Potassium, serum-high (hyperkalemia) ^† 1	25/222 (11.26%)	15/237 (6.33%)
Potassium, serum-low (hypokalemia) ^† 1	81/222 (36.49%)	92/237 (38.82%)
Sodium, serum-high (hypernatremia) ^† 1	17/222 (7.66%)	20/237 (8.44%)
Sodium, serum-low (hyponatremia) ^† 1	66/222 (29.73%)	84/237 (35.44%)
Musculoskeletal and connective tissue disorders
Muscle weakness, not d/t neuropathy - Extrem-lower ^† 1	15/222 (6.76%)	13/237 (5.49%)
Muscle weakness, not d/t neuropathy - body/general ^† 1	47/222 (21.17%)	57/237 (24.05%)
Musculoskeletal/Soft Tissue-Other ^† 1	22/222 (9.91%)	20/237 (8.44%)
Pain - Back ^† 1	91/222 (40.99%)	97/237 (40.93%)
Pain - Bone ^† 1	36/222 (16.22%)	44/237 (18.57%)
Pain - Chest wall ^† 1	11/222 (4.95%)	19/237 (8.02%)
Pain - Extremity-limb ^† 1	51/222 (22.97%)	73/237 (30.80%)
Pain - Joint ^† 1	66/222 (29.73%)	58/237 (24.47%)
Pain - Muscle ^† 1	51/222 (22.97%)	62/237 (26.16%)
Pain - Neck ^† 1	20/222 (9.01%)	17/237 (7.17%)
Nervous system disorders
Dizziness ^† 1	71/222 (31.98%)	86/237 (36.29%)
Memory impairment ^† 1	5/222 (2.25%)	14/237 (5.91%)
Neurology-Other ^† 1	15/222 (6.76%)	6/237 (2.53%)
Neuropathy: motor ^† 1	23/222 (10.36%)	52/237 (21.94%)
Neuropathy: sensory ^† 1	112/222 (50.45%)	173/237 (73.00%)
Pain - Head/headache ^† 1	35/222 (15.77%)	45/237 (18.99%)
Pain - Neuralgia/peripheral nerve ^† 1	5/222 (2.25%)	13/237 (5.49%)
Taste alteration (dysgeusia) ^† 1	56/222 (25.23%)	71/237 (29.96%)
Tremor ^† 1	30/222 (13.51%)	25/237 (10.55%)
Psychiatric disorders
Confusion ^† 1	20/222 (9.01%)	18/237 (7.59%)
Insomnia ^† 1	94/222 (42.34%)	99/237 (41.77%)
Mood alteration - anxiety ^† 1	43/222 (19.37%)	37/237 (15.61%)
Mood alteration - depression ^† 1	45/222 (20.27%)	41/237 (17.30%)
Renal and urinary disorders
Glomerular filtration rate ^† 1	12/222 (5.41%)	14/237 (5.91%)
Proteinuria ^† 1	15/222 (6.76%)	13/237 (5.49%)
Urinary frequency/urgency ^† 1	16/222 (7.21%)	12/237 (5.06%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis ^† 1	35/222 (15.77%)	28/237 (11.81%)
Cough ^† 1	77/222 (34.68%)	93/237 (39.24%)
Dyspnea (shortness of breath) ^† 1	86/222 (38.74%)	86/237 (36.29%)
Hemorrhage, pulmonary/upper respiratory - Nose ^† 1	19/222 (8.56%)	16/237 (6.75%)
Nasal cavity/paranasal sinus reactions ^† 1	13/222 (5.86%)	22/237 (9.28%)
Pain - Throat/pharynx/larynx ^† 1	6/222 (2.70%)	13/237 (5.49%)
Pulmonary/Upper Respiratory-Other ^† 1	14/222 (6.31%)	14/237 (5.91%)
Voice changes/dysarthria ^† 1	8/222 (3.60%)	19/237 (8.02%)
Skin and subcutaneous tissue disorders
Dermatology/Skin-Other ^† 1	23/222 (10.36%)	16/237 (6.75%)
Dry skin ^† 1	45/222 (20.27%)	41/237 (17.30%)
Hair loss/Alopecia (scalp or body) ^† 1	14/222 (6.31%)	20/237 (8.44%)
Pruritus/itching ^† 1	45/222 (20.27%)	23/237 (9.70%)
Rash/desquamation ^† 1	57/222 (25.68%)	56/237 (23.63%)
Rash: acne/acneiform ^† 1	9/222 (4.05%)	17/237 (7.17%)
Sweating (diaphoresis) ^† 1	27/222 (12.16%)	29/237 (12.24%)
Vascular disorders
Flushing ^† 1	27/222 (12.16%)	17/237 (7.17%)
Hot flashes/flushes ^† 1	16/222 (7.21%)	14/237 (5.91%)
Hypertension ^† 1	37/222 (16.67%)	35/237 (14.77%)
Hypotension ^† 1	18/222 (8.11%)	27/237 (11.39%)
Thrombosis/thrombus/embolism ^† 1	21/222 (9.46%)	22/237 (9.28%)
† 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:	SWOG Statistical Center
Phone:	206-667-4623

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

Unger JM, LeBlanc M, Blanke CD. The Effect of Positive SWOG Treatment Trials on Survival of Patients With Cancer in the US Population. JAMA Oncol. 2017 Oct 1;3(10):1345-1351. doi: 10.1001/jamaoncol.2017.0762.

Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X. Epub 2016 Dec 23.

Usmani SZ, Heuck C, Mitchell A, Szymonifka J, Nair B, Hoering A, Alsayed Y, Waheed S, Haider S, Restrepo A, Van Rhee F, Crowley J, Barlogie B. Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents. Haematologica. 2012 Nov;97(11):1761-7. doi: 10.3324/haematol.2012.065698. Epub 2012 Jun 11.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00644228
Other Study ID Numbers:	NCI-2009-00798 NCI-2009-00798 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) SWOG-S0777 S0777 CDR0000590321 S0777 ( Other Identifier: SWOG ) S0777 ( Other Identifier: CTEP ) U10CA180888 ( U.S. NIH Grant/Contract ) U10CA032102 ( U.S. NIH Grant/Contract )
First Submitted:	March 22, 2008
First Posted:	March 26, 2008
Results First Submitted:	April 20, 2017
Results First Posted:	July 6, 2017
Last Update Posted:	April 4, 2024

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