Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI SWOG-S0232 S0232, NCT00064038

Objectives

1. Compare the progression-free survival of patients with previously untreated stage I, II, or III multiple myeloma treated with dexamethasone with or without lenalidomide.
2. Compare the overall response rate in patients treated with these regimens.
3. Compare the major response rate (indicated by greater than 75% decrease in M-protein) in patients treated with these regimens.
4. Compare the overall survival and time to best response in patients treated with these regimens.
5. Compare the toxicity profile of these regimens, including thrombotic complications, in these patients.
6. Compare the effect of these regimens on gene expression and proteomic analysis in these patients.

Entry Criteria

Disease Characteristics:

• Previously untreated multiple myeloma
  • Stage I, II, or III disease by the International Staging System



• Measurable M-protein as defined by 1 of the following:
  • Serum M-protein at least 1.0 g/dL by serum protein electrophoresis or immunoelectrophoresis
  • Urinary M-protein excretion at least 200 mg/24 hours



• No nonsecretory multiple myeloma



• Not planning to undergo future autologous stem cell transplantation

Prior/Concurrent Therapy:

Biologic therapy

• No prior interferon or thalidomide

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Prior high-dose dexamethasone allowed provided duration of administration was no more than 4 days

Radiotherapy

• Prior localized radiotherapy allowed provided it was not to the sole site of evaluable disease

Surgery

• Not specified

Other

• No prior treatment for clinically significant ventricular cardiac arrhythmias
• Concurrent bisphosphonates allowed

Patient Characteristics:

Age

• 18 and over

Performance status

• Zubrod 0-3*

 [Note: *Zubrod 3 allowed only if multiple myeloma is the central cause of disability]

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 80,000/mm³*
• Absolute neutrophil count at least 1,000/mm³*
• Hemoglobin at least 9 g/dL* (epoetin alfa or transfusion allowed)

 [Note: *Unless due to greater than 50% marrow involvement by myeloma on biopsy]

Hepatic

• AST/ALT no greater than 3 times upper limit of normal*

 [Note: *Values outside of this range are allowed at the investigator's discretion]

Renal

• Creatinine no greater than 2.5 mg/dL*

 [Note: *Values outside of this range are allowed at the investigator's discretion]

Cardiovascular

• No New York Heart Association class III or IV heart failure
• No myocardial infarction within the past 6 months
• No poorly controlled hypertension

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 4 weeks before, during, and for 4 weeks after study treatment
  • Female patients must use 2 reliable forms of contraception simultaneously
  • Male patients must use effective barrier contraception
• No uncontrolled active infection requiring IV antibiotics
• No poorly controlled diabetes mellitus that would preclude ability to take oral glucocorticoids
• No other serious medical condition that would preclude study participation
• No psychiatric illness that would preclude study participation
• No other malignancy within the past 3 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• Must be able to take aspirin by mouth at a dose of 325 mg per day or enoxaparin subcutaneously at a dose of 40 mg per day as a form of thrombotic prophylaxis, except if already on therapeutic anticoagulant medication

Expected Enrollment

A total of 500 patients (250 per treatment arm) will be accrued for this study within 4 years.

Outcomes

Progression-free survival

Overall response rates
Major response rate as measured by a decrease in m-protein > 75%
Time to best response
Overall survival
Toxicity as measured by CTCAE v. 3.0
Biological endpoints including effects on gene expression and proteomic analysis at baseline and after 3 courses of treatment

Outline

This is a randomized, double-blind, crossover, multicenter study. Patients are stratified according to disease stage by the International Staging System (I vs II vs III) and Zubrod performance status (0-1 vs 2-3). Patients are randomized to 1 of 2 treatment arms.

Arm I

• Induction therapy: Patients receive 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.



• Maintenance therapy: Patients receive 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.

Arm II

• Induction therapy: Patients receive DM as in arm I induction and oral placebo on days 1-28. Treatment repeats as in arm I induction.

  Patients with responding or stable disease proceed to maintenance therapy. Patients with disease progression during induction therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy receive unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance.




• Maintenance therapy: Patients receive oral DM as in arm I maintenance and oral placebo on days 1-21. Courses repeat as in arm I maintenance.

  Patients with disease progression during maintenance therapy cross over and receive unblinded treatment with DM and lenalidomide as in arm I induction. Patients with responding or stable disease after unblinded induction therapy proceed to unblinded maintenance therapy with DM and lenalidomide as in arm I maintenance.

Patients are followed periodically for up to 5 years.

Zonder JA, Crowley JJ, Bolejack V, et al.: A randomized Southwest Oncology Group study comparing dexamethasone (D) to lenalidomide + dexamethasone (LD) as treatment of newly-diagnosed multiple myeloma (NDMM): impact of cytogenetic abnormalities on efficacy of LD, and updated overall study results. [Abstract] J Clin Oncol 26 (Suppl 15): A-8521, 2008.

Zonder JA, Crowley J, Hussein MA, et al.: Superiority of lenalidomide (Len) plus high-dose dexamethasone (HD) compared to HD alone as treatment of newly-diagnosed multiple myeloma (NDMM): results of the randomized, double-blinded, placebo-controlled SWOG trial S0232. [Abstract] Blood 110 (11): A-77, 2007.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Jeffrey Zonder, MD, Protocol chair		Ph: 313-576-8730; 800-527-6266 Email: zonderj@karmanos.org

Registry Information
Official Title		Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients with Previously Untreated Multiple Myeloma
Trial Start Date		2004-11-01
Registered in ClinicalTrials.gov		NCT00064038
Date Submitted to PDQ		2003-05-15
Information Last Verified		2008-01-16
NCI Grant/Contract Number		CA32102

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