Trial Outcomes & Findings for S0232 Dexamethasone With or Without Lenalidomide in Treating Patients With Previously Untreated Stage I, Stage II, or Stage III Multiple Myeloma (NCT NCT00064038)

Last Updated: 2015-03-25

Results Overview

Progression is defined as a \> 25% increase from baseline in myeloma protein production or other signs of disease progression such as hypercalcemia, etc. In patients with a confirmed Partial Remission, Remission, or Complete Remission, relapse is defined as the first occurrence of any of the following: 1) a myeloma protein increase by than 100% from the lowest level recorded on study, provided the absolute magnitude of this increase is at least 1g/dL for a serum monoclonal protein or at least 500 mg/24 hrs of urine M-protein; 2) a myeloma protein increase above the response criteria for Partial Remission, with the same requirements for the absolute magnitude of the protein increase; 3)reappearance of any myeloma peak that had disappeared while on protocol treatment, provided it meets the same requirements listed above; 4) increase in the size and number of lytic bone lesions recognized on radiographs.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

198 participants

Primary outcome timeframe

From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years

Results posted on

2015-03-25

Participant Flow

Between October 15, 2004 and April 2, 2007, 198 patients were enrolled at 41 cooperative medical institutions.

Participant milestones

Participant milestones
Measure	Lenalidomide+Dexamethasone Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Crossover to Lenalidomide+Dexamethasone Patients who have progressive or relapsed disease or who experience unacceptable toxicity attributable to dexamethasone dosing level -2 while on blinded treatment, will be unblinded. Patients shown to have been randomized to DEX + Placebo will proceed with crossover registration and Open-Label Induction with DEX + CC-5013or with open-label CC-5013 alone if they are unblinded due to dexamethasone toxicity. Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Initial Randomization STARTED	100	98	0
Initial Randomization Eligible and Analyzable	97	95	0
Initial Randomization Safety Population	96	94	0
Initial Randomization COMPLETED	0	0	0
Initial Randomization NOT COMPLETED	100	98	0
Crossover to Lenalidomide+Dexamethasone STARTED	0	0	42
Crossover to Lenalidomide+Dexamethasone Eligible and Analyzable	0	0	40
Crossover to Lenalidomide+Dexamethasone Safety Population	0	0	40
Crossover to Lenalidomide+Dexamethasone COMPLETED	0	0	40
Crossover to Lenalidomide+Dexamethasone NOT COMPLETED	0	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

S0232 Dexamethasone With or Without Lenalidomide in Treating Patients With Previously Untreated Stage I, Stage II, or Stage III Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenalidomide+Dexamethasone n=97 Participants Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone n=95 Participants Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Total n=192 Participants Total of all reporting groups
Age, Continuous Overall	64.9 years n=5 Participants	63.1 years n=7 Participants	64.6 years n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	40 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	55 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years

Outcome measures

Outcome measures
Measure	Lenalidomide and Dexamethasone n=97 Participants Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone n=95 Participants Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Crossover to Rev+Dex Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression-Free Survival	78 percentage of participants Interval 70.0 to 78.0	52 percentage of participants Interval 41.0 to 62.0	—

SECONDARY outcome

Timeframe: From time of initiating study treatment until discontinuation of study treatment or of open-label REVLIMID + LOW DOSE DEX, whichever comes last, up to 5 years

Population: All participants receiving at least one dose of induction therapy

Compare the toxicity profile of these regimens, including thrombotic complications, in these patients, based on CTCAE v. 3.0.

Outcome measures

Outcome measures
Measure	Lenalidomide and Dexamethasone n=96 Participants Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone n=94 Participants Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Crossover to Rev+Dex n=40 Participants Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Toxicity Thrombotic microangiopathy	1 Participants	0 Participants	0 Participants
Toxicity Thyroid function, low (hypothyroidism)	1 Participants	0 Participants	0 Participants
Toxicity ALT, SGPT (serum glutamic pyruvic transaminase)	1 Participants	1 Participants	0 Participants
Toxicity AST, SGOT	2 Participants	0 Participants	0 Participants
Toxicity Albumin, serum-low (hypoalbuminemia)	1 Participants	0 Participants	2 Participants
Toxicity Anorexia	2 Participants	1 Participants	1 Participants
Toxicity Apnea	1 Participants	0 Participants	0 Participants
Toxicity Arthritis (non-septic)	1 Participants	0 Participants	0 Participants
Toxicity Aspiration	1 Participants	0 Participants	0 Participants
Toxicity Ataxia (incoordination)	0 Participants	1 Participants	0 Participants
Toxicity Bilirubin (hyperbilirubinemia)	0 Participants	0 Participants	1 Participants
Toxicity CNS cerebrovascular ischemia	1 Participants	2 Participants	2 Participants
Toxicity Calcium, serum-high (hypercalcemia)	0 Participants	1 Participants	0 Participants
Toxicity Calcium, serum-low (hypocalcemia)	7 Participants	2 Participants	3 Participants
Toxicity Cardiopulmonary arrest, cause unknown (non-fatal)	1 Participants	0 Participants	0 Participants
Toxicity Cataract	1 Participants	1 Participants	2 Participants
Toxicity Cognitive disturbance	1 Participants	1 Participants	0 Participants
Toxicity Colitis	0 Participants	0 Participants	1 Participants
Toxicity Colitis, infectious (e.g., Clostridium difficile)	0 Participants	0 Participants	1 Participants
Toxicity Confusion	1 Participants	0 Participants	0 Participants
Toxicity Constipation	0 Participants	2 Participants	1 Participants
Toxicity Creatinine	0 Participants	0 Participants	1 Participants
Toxicity Cystitis	0 Participants	1 Participants	0 Participants
Toxicity Dehydration	1 Participants	0 Participants	3 Participants
Toxicity Dermatology/Skin-Other (Specify)	0 Participants	1 Participants	0 Participants
Toxicity Diarrhea	5 Participants	1 Participants	1 Participants
Toxicity Dizziness	1 Participants	1 Participants	2 Participants
Toxicity Dyspnea (shortness of breath)	4 Participants	2 Participants	0 Participants
Toxicity Edema: limb	0 Participants	1 Participants	2 Participants
Toxicity Encephalopathy	0 Participants	0 Participants	1 Participants
Toxicity Fatigue (asthenia, lethargy, malaise)	19 Participants	12 Participants	8 Participants
Toxicity Febrile neutropenia	1 Participants	0 Participants	1 Participants
Toxicity Fever in absence of neutropenia, ANC lt1.0x10e9/L	1 Participants	1 Participants	0 Participants
Toxicity Fracture	0 Participants	1 Participants	0 Participants
Toxicity Gastritis (including bile reflux gastritis)	0 Participants	0 Participants	1 Participants
Toxicity Gastrointestinal-Other (Specify)	1 Participants	0 Participants	0 Participants
Toxicity Glomerular filtration rate	0 Participants	0 Participants	1 Participants
Toxicity Glucose, serum-high (hyperglycemia)	5 Participants	18 Participants	2 Participants
Toxicity Glucose, serum-low (hypoglycemia)	1 Participants	0 Participants	0 Participants
Toxicity Heartburn/dyspepsia	0 Participants	1 Participants	0 Participants
Toxicity Hemoglobin	6 Participants	5 Participants	6 Participants
Toxicity Hemorrhage, CNS	1 Participants	0 Participants	0 Participants
Toxicity Hemorrhage, GI - Colon	1 Participants	0 Participants	0 Participants
Toxicity Hypertension	0 Participants	3 Participants	0 Participants
Toxicity Hypotension	3 Participants	0 Participants	0 Participants
Toxicity Hypoxia	4 Participants	1 Participants	1 Participants
Toxicity INR (of prothrombin time)	1 Participants	2 Participants	0 Participants
Toxicity Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1 Participants	0 Participants	1 Participants
Toxicity Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus	1 Participants	0 Participants	0 Participants
Toxicity Inf (clin/microbio) w/Gr 3-4 neuts - Lung	5 Participants	0 Participants	0 Participants
Toxicity Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest	1 Participants	0 Participants	0 Participants
Toxicity Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	1 Participants	2 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	2 Participants	0 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	0 Participants	1 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Colon	1 Participants	1 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1 Participants	3 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Skin	2 Participants	1 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - UTI	2 Participants	2 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	3 Participants	1 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils - Wound	1 Participants	0 Participants	0 Participants
Toxicity Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran	0 Participants	0 Participants	1 Participants
Toxicity Infection with unknown ANC - Lung (pneumonia)	1 Participants	0 Participants	0 Participants
Toxicity Infection with unknown ANC - Upper airway NOS	1 Participants	1 Participants	0 Participants
Toxicity Infection-Other (Specify)	0 Participants	1 Participants	0 Participants
Toxicity Insomnia	4 Participants	6 Participants	0 Participants
Toxicity Joint-function	1 Participants	0 Participants	0 Participants
Toxicity Left ventricular diastolic dysfunction	0 Participants	0 Participants	1 Participants
Toxicity Left ventricular systolic dysfunction	1 Participants	0 Participants	0 Participants
Toxicity Leukocytes (total WBC)	14 Participants	5 Participants	4 Participants
Toxicity Lymphopenia	10 Participants	5 Participants	8 Participants
Toxicity Mood alteration - agitation	1 Participants	1 Participants	1 Participants
Toxicity Mood alteration - anxiety	1 Participants	1 Participants	0 Participants
Toxicity Mood alteration - depression	11 Participants	8 Participants	2 Participants
Toxicity Mucositis/stomatitis (clinical exam) - Oral cavity	0 Participants	1 Participants	0 Participants
Toxicity Muscle weakness, not d/t neuropathy - Extrem-lower	1 Participants	3 Participants	1 Participants
Toxicity Muscle weakness, not d/t neuropathy - body/general	9 Participants	4 Participants	3 Participants
Toxicity Musculoskeletal/Soft Tissue-Other (Specify)	0 Participants	2 Participants	0 Participants
Toxicity Nausea	2 Participants	1 Participants	0 Participants
Toxicity Neuropathy: motor	0 Participants	1 Participants	0 Participants
Toxicity Neuropathy: sensory	3 Participants	4 Participants	0 Participants
Toxicity Neutrophils/granulocytes (ANC/AGC)	21 Participants	6 Participants	7 Participants
Toxicity Ocular/Visual-Other (Specify)	1 Participants	0 Participants	1 Participants
Toxicity Ophthalmoplegia/diplopia (double vision)	0 Participants	1 Participants	0 Participants
Toxicity Opportunistic inf associated w/gt=Gr 2 lymphopenia	2 Participants	0 Participants	1 Participants
Toxicity PTT (Partial thromboplastin time)	0 Participants	1 Participants	0 Participants
Toxicity Pain - Abdomen NOS	0 Participants	2 Participants	0 Participants
Toxicity Pain - Back	1 Participants	2 Participants	1 Participants
Toxicity Pain - Bladder	0 Participants	0 Participants	1 Participants
Toxicity Pain - Bone	1 Participants	3 Participants	0 Participants
Toxicity Pain - Extremity-limb	1 Participants	0 Participants	0 Participants
Toxicity Pain - Head/headache	0 Participants	1 Participants	0 Participants
Toxicity Pain - Joint	3 Participants	1 Participants	0 Participants
Toxicity Pain - Muscle	3 Participants	1 Participants	1 Participants
Toxicity Pain - Pain NOS	1 Participants	0 Participants	0 Participants
Toxicity Pain - Stomach	0 Participants	1 Participants	0 Participants
Toxicity Pain-Other (Specify)	0 Participants	1 Participants	1 Participants
Toxicity Pancreatic endocrine: glucose intolerance	0 Participants	1 Participants	0 Participants
Toxicity Perforation, GI - Colon	1 Participants	0 Participants	0 Participants
Toxicity Perforation, GI - Small bowel NOS	0 Participants	1 Participants	0 Participants
Toxicity Phosphate, serum-low (hypophosphatemia)	5 Participants	4 Participants	2 Participants
Toxicity Platelets	7 Participants	4 Participants	3 Participants
Toxicity Pneumonitis/pulmonary infiltrates	3 Participants	2 Participants	2 Participants
Toxicity Potassium, serum-low (hypokalemia)	6 Participants	2 Participants	3 Participants
Toxicity Prolonged QTc interval	1 Participants	0 Participants	0 Participants
Toxicity Proteinuria	1 Participants	0 Participants	0 Participants
Toxicity Pulmonary/Upper Respiratory-Other (Specify)	1 Participants	0 Participants	0 Participants
Toxicity Rash/desquamation	1 Participants	1 Participants	1 Participants
Toxicity Rash: acne/acneiform	0 Participants	1 Participants	1 Participants
Toxicity Rash: erythema multiforme	0 Participants	0 Participants	1 Participants
Toxicity Renal failure	0 Participants	1 Participants	2 Participants
Toxicity SVT and nodal arrhythmia - Atrial fibrillation	0 Participants	2 Participants	0 Participants
Toxicity Sodium, serum-high (hypernatremia)	0 Participants	1 Participants	0 Participants
Toxicity Sodium, serum-low (hyponatremia)	3 Participants	2 Participants	3 Participants
Toxicity Somnolence/depressed level of consciousness	0 Participants	0 Participants	1 Participants
Toxicity Speech impairment (e.g., dysphasia or aphasia)	0 Participants	0 Participants	1 Participants
Toxicity Syncope (fainting)	1 Participants	0 Participants	0 Participants
Toxicity Thrombosis/embolism (vascular access-related)	2 Participants	0 Participants	0 Participants
Toxicity Thrombosis/thrombus/embolism	19 Participants	5 Participants	5 Participants
Toxicity Tinnitus	1 Participants	0 Participants	0 Participants
Toxicity Vision-blurred vision	2 Participants	3 Participants	1 Participants
Toxicity Vomiting	2 Participants	1 Participants	0 Participants
Toxicity Weight loss	0 Participants	0 Participants	1 Participants

Adverse Events

Lenalidomide and Dexamethasone

Serious events: 41 serious events

Other events: 91 other events

Deaths: 0 deaths

Dexamethasone

Serious events: 21 serious events

Other events: 90 other events

Deaths: 0 deaths

Crossover to Rev+Dex

Serious events: 14 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Robert Z. Orlowski, MD, PhD

SWOG

Phone: (713) 792-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Lenalidomide and Dexamethasone n=96 participants at risk Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone n=94 participants at risk Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Crossover to Rev+Dex n=40 participants at risk Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Hemoglobin	3.1% 3/96 • Report through 1/13/2009 to match data reported in MS.	2.1% 2/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Cardiac General-Other (Specify)	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Cardiac-ischemia/infarction	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Left ventricular diastolic dysfunction	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Left ventricular systolic dysfunction	3.1% 3/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Supraventricular (SVT) and nodal arrhythmia - Atrial fibrillation	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	2.1% 2/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders SVT and nodal arrhythmia - Atrial tachycardia/paroxysmal atrial tachycardia (PAT)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Eye disorders Ocular/Visual-Other (Specify)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Eye disorders Vision-blurred vision	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Colitis	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Constipation	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Diarrhea	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Fistula, GI - Abdomen, not otherwise specified (NOS)	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Fistula, GI - Colon/cecum/appendix	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Gastrointestinal-Other (Specify)	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Hemorrhage, GI - Colon	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Hemorrhage, GI - Lower GI NOS	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Nausea	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Obstruction, GI - Colon	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	2.5% 1/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Pain - Abdomen NOS	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	2.1% 2/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Perforation, GI - Colon	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Stricture/stenosis (incl anastomotic), Esophagus	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Vomiting	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Death not associated with CTCAE term - Death, not otherwise specified (NOS)	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Edema: limb	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Extremity-lower (gait/walking)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Fatigue (asthenia, lethargy, malaise)	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	2.1% 2/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Pain - Pain NOS	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Sudden death	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Hepatobiliary disorders Cholecystitis	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf (clin/microbio) w/Gr 3-4 neuts - Blood	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf (clin/microbio) w/Gr 3-4 neuts - Lung	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf (clin/microbio) w/Gr 3-4 neuts - Up aerodigest	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal absolute neutrophil count (ANC) or Gr 1-2 neutrophils - Ab NOS	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Colon	1.0% 1/96 • Report through 1/13/2009 to match data reported in MS.	1.1% 1/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Lung	2.1% 2/96 • Report through 1/13/2009 to match data reported in MS.	2.1% 2/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.

Other adverse events
Measure	Lenalidomide and Dexamethasone n=96 participants at risk Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Dexamethasone n=94 participants at risk Patients receive induction therapy comprising DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction. Some patients may then receive maintenance therapy comprising oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.	Crossover to Rev+Dex n=40 participants at risk Patients receive induction therapy comprising oral dexamethasone (DM) on days 1-4, 9-12, and 17-20 and oral lenalidomide on days 1-28. Treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising oral DM on days 1-4 and 15-18 and oral lenalidomide on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Hemoglobin	64.6% 62/96 • Report through 1/13/2009 to match data reported in MS.	67.0% 63/94 • Report through 1/13/2009 to match data reported in MS.	77.5% 31/40 • Report through 1/13/2009 to match data reported in MS.
Cardiac disorders Palpitations	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Ear and labyrinth disorders Tinnitus	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Eye disorders Cataract	6.2% 6/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
Eye disorders Ocular/Visual-Other (Specify)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Eye disorders Vision-blurred vision	12.5% 12/96 • Report through 1/13/2009 to match data reported in MS.	9.6% 9/94 • Report through 1/13/2009 to match data reported in MS.	12.5% 5/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Constipation	44.8% 43/96 • Report through 1/13/2009 to match data reported in MS.	36.2% 34/94 • Report through 1/13/2009 to match data reported in MS.	47.5% 19/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Diarrhea	45.8% 44/96 • Report through 1/13/2009 to match data reported in MS.	30.9% 29/94 • Report through 1/13/2009 to match data reported in MS.	22.5% 9/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Distention/bloating, abdominal	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	8.5% 8/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Heartburn/dyspepsia	18.8% 18/96 • Report through 1/13/2009 to match data reported in MS.	12.8% 12/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	7.3% 7/96 • Report through 1/13/2009 to match data reported in MS.	10.6% 10/94 • Report through 1/13/2009 to match data reported in MS.	12.5% 5/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Mucositis/stomatitis (functional/symp) - Oral cav	7.3% 7/96 • Report through 1/13/2009 to match data reported in MS.	11.7% 11/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Nausea	37.5% 36/96 • Report through 1/13/2009 to match data reported in MS.	25.5% 24/94 • Report through 1/13/2009 to match data reported in MS.	27.5% 11/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Pain - Abdomen, not otherwise specified (NOS)	9.4% 9/96 • Report through 1/13/2009 to match data reported in MS.	7.4% 7/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Pain - Dental/teeth/peridontal	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
Gastrointestinal disorders Vomiting	11.5% 11/96 • Report through 1/13/2009 to match data reported in MS.	10.6% 10/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Edema: head and neck	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	13.8% 13/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Edema: limb	37.5% 36/96 • Report through 1/13/2009 to match data reported in MS.	37.2% 35/94 • Report through 1/13/2009 to match data reported in MS.	32.5% 13/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Fatigue (asthenia, lethargy, malaise)	77.1% 74/96 • Report through 1/13/2009 to match data reported in MS.	75.5% 71/94 • Report through 1/13/2009 to match data reported in MS.	77.5% 31/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Fever in absence of neutropenia, ANC lt1.0x10e9/L	7.3% 7/96 • Report through 1/13/2009 to match data reported in MS.	16.0% 15/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Pain - Chest/thorax NOS	8.3% 8/96 • Report through 1/13/2009 to match data reported in MS.	8.5% 8/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Pain-Other (Specify)	5.2% 5/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
General disorders Rigors/chills	6.2% 6/96 • Report through 1/13/2009 to match data reported in MS.	8.5% 8/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal absolute neutrophil count (ANC) or Gr 1-2 neutrophils - Bronchus	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	7.5% 3/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Lung	5.2% 5/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Skin	9.4% 9/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - UTI	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	10.0% 4/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	24.0% 23/96 • Report through 1/13/2009 to match data reported in MS.	16.0% 15/94 • Report through 1/13/2009 to match data reported in MS.	12.5% 5/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Infection with unknown ANC - Sinus	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Infection with unknown ANC - Skin (cellulitis)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Infection with unknown ANC - Upper airway, not otherwise specified (NOS)	6.2% 6/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/40 • Report through 1/13/2009 to match data reported in MS.
Infections and infestations Infection with unknown ANC - Urinary tract NOS	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Injury, poisoning and procedural complications Bruising (in absence of Gr 3-4 thrombocytopenia)	0.00% 0/96 • Report through 1/13/2009 to match data reported in MS.	0.00% 0/94 • Report through 1/13/2009 to match data reported in MS.	5.0% 2/40 • Report through 1/13/2009 to match data reported in MS.
Investigations Alanine aminotransferase (ALT), serum glutamic pyruvic transaminase (SGPT)	17.7% 17/96 • Report through 1/13/2009 to match data reported in MS.	14.9% 14/94 • Report through 1/13/2009 to match data reported in MS.	10.0% 4/40 • Report through 1/13/2009 to match data reported in MS.
Investigations Aspartate aminotransferase (AST), serum glutamic oxaloacetic transaminase (SGOT)	12.5% 12/96 • Report through 1/13/2009 to match data reported in MS.	11.7% 11/94 • Report through 1/13/2009 to match data reported in MS.	17.5% 7/40 • Report through 1/13/2009 to match data reported in MS.
Investigations Alkaline phosphatase	17.7% 17/96 • Report through 1/13/2009 to match data reported in MS.	10.6% 10/94 • Report through 1/13/2009 to match data reported in MS.	10.0% 4/40 • Report through 1/13/2009 to match data reported in MS.
Investigations Bilirubin (hyperbilirubinemia)	10.4% 10/96 • Report through 1/13/2009 to match data reported in MS.	5.3% 5/94 • Report through 1/13/2009 to match data reported in MS.	10.0% 4/40 • Report through 1/13/2009 to match data reported in MS.