RATIONALE: Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving thalidomide before and after peripheral stem cell transplantation may be effective in treating newly diagnosed multiple myeloma.

PURPOSE: Phase II trial to study the effectiveness of combining thalidomide with chemotherapy and peripheral stem cell transplantation in treating patients who have newly diagnosed multiple myeloma.

Condition	Treatment or Intervention	Phase
stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma	Drug: cyclophosphamide  Drug: dexamethasone  Drug: filgrastim  Drug: melphalan  Drug: prednisone  Drug: sargramostim  Drug: thalidomide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: growth factor antagonist therapy  Procedure: peripheral blood stem cell transplantation	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy and toxicity of thalidomide and dexamethasone as a pre-transplantation induction regimen in patients with multiple myeloma.
• Determine, preliminarily, the safety and efficacy of prednisone and thalidomide maintenance therapy in these patients.
• Correlate chromosome 13 abnormalities with therapeutic response in patients treated with this regimen.
• Correlate specific subsets of chromosome aberrations with event-free and overall survival of patients treated with this regimen.
• Evaluate immune reconstitution and recovery after first and second transplantation in these patients.

OUTLINE: This is a multicenter study.

• Induction chemotherapy: Patients receive oral thalidomide once daily on days 1-35 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 35 days for 3 courses in the absence of disease progression or unacceptable toxicity.
• Stem cell mobilization and collection: Beginning 5-7 days, but no more than 3 weeks, after completion of induction chemotherapy, patients receive cyclophosphamide IV over 45-60 minutes on day 0, filgrastim (G-CSF) subcutaneously (SC) on days 1-10, and sargramostim (GM-CSF) SC beginning on day 1 and continuing until completion of peripheral blood stem cell (PBSC) collection. Patients begin PBSC collection on day 11 or as soon as blood counts recover.
• First transplantation: Within 3-6 weeks after cyclophosphamide administration, patients receive melphalan IV over 20 minutes on day -1. Patients undergo PBSC infusion on day 0. Patients receive GM-CSF SC or IV beginning on day 6 and continuing until blood counts recover.
• Second transplantation: Between 2-4 months after first transplantation, patients undergo a second tandem melphalan and PBSC transplantation with GM-CSF support as above.
• Maintenance therapy: Beginning 70-90 days post-transplantation, patients receive oral prednisone every other day and oral thalidomide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 5 years.

PROJECTED ACCRUAL: Approximately 99 patients will be accrued for this study within 18 months.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Newly diagnosed multiple myeloma requiring treatment
• Smoldering myeloma with evidence of progressive disease requiring chemotherapy
• More than 25% increase in M component levels and/or Bence-Jones excretion or symptom development
• Non-secretory patients with at least 30% bone marrow plasmacytosis
• No IgM peaks unless there is evidence of more than 30% bone marrow plasmacytosis or more than 3 lytic lesions

PATIENT CHARACTERISTICS: Age

• 18 to 65

Performance status

• Zubrod 0-2 OR
• Zubrod 3-4 based solely on bone pain

Life expectancy

• Not specified

Hematopoietic

• No untreated, unresolved symptomatic hyperviscosity

Hepatic

• Hepatitis B negative

Renal

• Creatinine no greater than 3 mg/dL if in renal failure and on dialysis (after hydration and/or correction of hypercalcemia)

Cardiovascular

• No history of chronic cerebrovascular accident
• No myocardial infarction within the past 6 months
• No unstable angina
• No congestive heart failure that is difficult to control
• No uncontrollable hypertension
• No cardiac arrhythmia that is difficult to control

Pulmonary

• No history of chronic obstructive or chronic restrictive pulmonary disease
• No untreated, unresolved pneumonia
• Pulmonary function tests (PFTs) at least 50% of predicted
• DLCO at least 50% of predicted
• Arterial partial pressure of oxygen greater than 70 if unable to complete PFTs due to bone pain or fracture

Other

• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No untreated, unresolved pathologic fractures
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use at least 2 highly effective methods of contraception for 4 weeks before, during, and for at least 4 weeks after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• No more than 8 weeks of prior thalidomide therapy

Chemotherapy

• No prior chemotherapy for this disease

Endocrine therapy

• Prior steroid therapy allowed provided treatment duration was no more than 2 weeks

Radiotherapy

• No prior radiotherapy to more than 50% of the pelvis

Surgery

• Not specified

Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      Banner Good Samaritan Medical Center, Phoenix,  Arizona,  85006,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange,  California,  92868,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      John Muir Comprehensive Cancer Center at John Muir Medical Center, Walnut Creek,  California,  94598,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1678,  United States; Recruiting
      Scripps Cancer Center at Scripps Clinic, La Jolla,  California,  92037-1027,  United States; Recruiting
      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5408,  United States; Recruiting
      Sutter Cancer Center, Sacramento,  California,  95816,  United States; Recruiting
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
      Charles B. Eberhart Cancer Center at DeKalb Medical Center, Decatur,  Georgia,  30033,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Idaho
      Mountain States Tumor Institute - Boise, Boise,  Idaho,  83712,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
Indiana
      Indiana Blood and Marrow Transplantation, Beech Grove,  Indiana,  46107,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      New Orleans Cancer Institute At Memorial Medical Center, New Orleans,  Louisiana,  70115,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States; Recruiting
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
      Providence Cancer Institute at Providence Hospital - Southfield, Southfield,  Michigan,  48075,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0948,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Saint Louis University Cancer Center, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      NYU Cancer Institute at New York University Medical Center, New York,  New York,  10016,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Southwest Cancer and Research Center at University Medical Center, Lubbock,  Texas,  79415-3364,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      Wilford Hall Medical Center, Lackland Air Force Base,  Texas,  78236-5300,  United States; Recruiting
Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84132,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
      Swedish Cancer Institute at Swedish Medical Center - First Hill Campus, Seattle,  Washington,  98104,  United States; Recruiting

Study chairs or principal investigators

Mohamad Ahmed Hussein, MD,  Study Chair,  Cleveland Clinic Cancer Center   

Study ID Numbers:  CDR0000069421; SWOG-S0204; NCT00040937
Record last reviewed:  September 2004
Last Updated:  April 4, 2005
Record first received:  July 8, 2002
ClinicalTrials.gov Identifier:  NCT00040937
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08