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

March 5, 2015 updated by: Southwest Oncology Group

Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients With Previously Untreated Multiple Myeloma

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

198

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • William Beaumont Hospital - Royal Oak Campus
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists at UCS Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: dexamethasone
Given orally
Drug: lenalidomide
Given orally
Active Comparator: 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.
Drug: dexamethasone
Given orally
Other: placebo
Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: From date of initial registration to date of progression/relapse of disease or death from any cause, whichever came first, up to 5 years

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity
Time Frame: 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
Compare the toxicity profile of these regimens, including thrombotic complications, in these patients, based on CTCAE v. 3.0.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2004

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

July 8, 2003

First Submitted That Met QC Criteria

July 8, 2003

First Posted (Estimate)

July 9, 2003

Study Record Updates

Last Update Posted (Estimate)

March 25, 2015

Last Update Submitted That Met QC Criteria

March 5, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S0232 (Other Identifier: SWOG)
  • U10CA032102 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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