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

NCT00064038 | Completed Phase 3 Results DMC

• 2 other identifiers: S0232U10CA032102
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Myeloma; Plasma Cell Neoplasm

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  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 Outcomes (1)

• Toxicity

  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

Study Arms (2)

Arm I

EXPERIMENTAL

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; Drug: lenalidomide

Arm II

ACTIVE COMPARATOR

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; Other: placebo

Interventions

dexamethasone DRUG

Given orally

Arm I; Arm II

lenalidomide DRUG

Given orally

Arm I

placebo OTHER

Given orally

Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, 48073, United States

Location

Utah Cancer Specialists at UCS Cancer Center

Salt Lake City, Utah, 84106, United States

Location

Related Publications (3)

• 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.

  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.

  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.

  PMID: 20876454 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Dexamethasone; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Robert Z. Orlowski, MD, PhD
• Organization: SWOG

rorlowsk@mdanderson.org

(713) 792-2860

Study Officials

• Jeffrey A. Zonder, MD

  Barbara Ann Karmanos Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2003
• First Posted: July 9, 2003
• Study Start: November 1, 2004
• Primary Completion: October 1, 2008
• Study Completion: May 1, 2012
• Last Updated: March 25, 2015
• Results First Posted: July 17, 2013

Record last verified: 2015-03

Locations

US (2)