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

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Southwest Oncology Group
ClinicalTrials.gov Identifier:	NCT00064038

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Drug: dexamethasone Drug: lenalidomide Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Phase III Trial Comparing Dexamethasone (DEX) to the Combination of DEX + CC-5013 in Patients With Previously Untreated Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Dexamethasone Dexamethasone acetate Doxiproct plus Lenalidomide CC 5013 Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall response rates [ Designated as safety issue: No ]
Major response rate as measured by a decrease in m-protein > 75% [ Designated as safety issue: No ]
Time to best response [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Toxicity as measured by CTCAE v. 3.0 [ Designated as safety issue: Yes ]
Biological endpoints including effects on gene expression and proteomic analysis at baseline and after 3 courses of treatment [ Designated as safety issue: No ]

Estimated Enrollment:	500
Study Start Date:	November 2004
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064038

Locations

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

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Jeffrey A. Zonder, MD

Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2010 Sep 27.

Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00064038 History of Changes
Other Study ID Numbers:	CDR0000306449, U10CA032102, S0232
Study First Received:	July 8, 2003
Last Updated:	July 19, 2011
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:

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

Additional relevant MeSH terms:

Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 12, 2012