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

NCT ID: NCT00064038

Last Updated: 2015-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 198 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30
• Study Completion Date: 2012-05-31

Brief Summary

RATIONALE: Drugs used in chemotherapy such as dexamethasone use different ways to stop cancer cells from dividing so they stop growing or die. Lenalidomide may stop the growth of multiple myeloma by stopping blood flow to the tumor. It is not yet known whether dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying dexamethasone and lenalidomide to see how well they work compared to dexamethasone alone in treating patients with previously untreated stage I, stage II, or stage III multiple myeloma.

Detailed Description

OBJECTIVES:

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

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.

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

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

dexamethasone

Intervention Type: DRUG

Given orally

lenalidomide

Intervention Type: DRUG

Given orally

Arm II

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.

Group Type: ACTIVE_COMPARATOR

dexamethasone

Intervention Type: DRUG

Given orally

placebo

Intervention Type: OTHER

Given orally

Interventions

dexamethasone

Given orally

Intervention Type: DRUG

lenalidomide

Given orally

Intervention Type: DRUG

placebo

Given orally

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

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/mm^3*
• Absolute neutrophil count at least 1,000/mm^3*
• 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey A. Zonder, MD

Role: STUDY_CHAIR

Barbara Ann Karmanos Cancer Institute

Locations

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, United States

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF Sr, Whittenberger BF, Abidi MH, Durie BG, Barlogie B. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood. 2010 Dec 23;116(26):5838-41. doi: 10.1182/blood-2010-08-303487. Epub 2010 Sep 27.

Reference Type: DERIVED

PMID: 20876454 (View on PubMed)

Other Identifiers

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0232

Identifier Type: OTHER

Identifier Source: secondary_id

S0232

Identifier Type: -

Identifier Source: org_study_id