RATIONALE: Drugs used in chemotherapy use different ways to stop tumor 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 and kill more tumor cells. Interferon alfa may interfere with the growth of the cancer cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose melphalan plus peripheral stem cell transplantation followed by interferon alfa in treating patients with Waldenstrom's macroglobulinemia.

Condition	Treatment or Intervention	Phase
Waldenstrom's Macroglobulinemia	Drug: dexamethasone  Drug: filgrastim  Drug: interferon alfa  Drug: melphalan	Phase II

Further Study Details: 

OBJECTIVES: I. Assess remission rates and overall and progression-free survival in patients with Waldenstrom's macroglobulinemia treated with tandem high dose melphalan supported by peripheral blood stem cell support.

II. Assess the associated hematologic and nonhematologic toxicities of this regimen in these patients.

PROTOCOL OUTLINE: Regimen A (dexamethasone induction): All patients receive high dose dexamethasone orally on days 1-4, 9-12, and 17-20; courses repeat every 35 days for a total of 3 courses.

Regimen B (stem cell mobilization and collection): Following a 4-6 week break after dexamethasone induction and regardless of response or progression, patients have stem cells collected following administration of filgrastim (G-CSF) by injection; G-CSF continues until completion of stem cell collection (maximum of 6 aphereses).

Regimen C (first peripheral blood stem cell transplant (PBSCT)): Regardless of disease progression, patients recovered from toxicities from dexamethasone induction and stem cell mobilization and collection, and who have adequate number of CD34 cells collected for at least 1 transplant, receive 1 dose of melphalan daily for 2 days followed by peripheral stem cell reinfusion. G-CSF is given by injection beginning on the day after peripheral stem cell reinfusion and continues until the absolute granulocyte count is greater than 1,000/mm3 on 3 consecutive days.

Regimen D (second PBSCT): Patients who had adequate stem cell collection for 2 transplants during regimen B, have no evidence of disease progression after the first transplant, and have recovered from effects of previous treatment undergo a second treatment with high dose melphalan with PBSCT and G-CSF support, given 3-12 months following the first transplant. Patients who had enough cells collected for only one transplant go directly to regimen E.

Regimen E (maintenance interferon alfa): Beginning 5-12 weeks after transplant and upon hematologic recovery of blood counts and other toxicities, patients with at least a partial response after high dose melphalan and PBSCT receive subcutaneous interferon alfa injections 3 times a week for 5 years or until disease progression, relapse, or toxicity.

Patients are followed every month for 6 months, then every 3 months for 5 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study over 4 years.

Ages Eligible for Study:  up to  69 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Immunologically diagnosed Waldenstrom's macroglobulinemia (WM)
• Evaluable quantifiable IgM
• One of the following criteria must be met: 1) Patient demonstrates clinical symptoms such as fatigue, dizziness, visual inacuity, or hemorrhagic manifestations of WM with anemia, hyperviscosity, thrombocytopenia, or coagulopathies; 2) Advanced tumor mass present involving ONE of the following: Extensive lymphadenopathy (greater than 2 cm); Hepato or splenomegaly palpable on clinical examination; Marked bone marrow infiltration greater than 50%; 3) Progressive disease; i.e., increase in IgM concentration by at least 50%, and/or a drop of greater than 2 g/dL in hemoglobin (in the absence of gastrointestinal bleeding), and/or a greater than 50,000/mm3 decrease in platelets

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: At least 4 weeks since chemotherapy and recovered
• Endocrine therapy: Not specified
• Radiotherapy: At least 4 weeks since radiotherapy and recovered
• Surgery: Not specified

--Patient Characteristics--

• Age: Under 70
• Performance status: SWOG 0-2
• Life expectancy: Not specified
• Hematopoietic: See Disease Characteristics
• Hepatic: Not specified
• Renal: Not specified
• Cardiovascular: At least 6 months since myocardial infarction; No congestive heart failure; No arrhythmia refractory to therapy; Ejection fraction within normal range by MUGA or ECHO
• Pulmonary: FEV1 at least 50% of predicted; DLCO at least 50% of predicted
• Other: Not pregnant or nursing; Effective contraception required of fertile patients; No significant comorbid condition; No uncontrolled life-threatening infection; No uncontrolled diabetes; No other malignancy within past 5 years except adequately treated basal or squamous cell skin cancer, carcinoma in situ of the cervix or adequately treated stage I or II cancer currently in remission; HIV negative; Hepatitis B surface antigen negative

Alabama
      MBCCOP - University of South Alabama, Mobile,  Alabama,  36688,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
      Veterans Affairs Medical Center - Phoenix (Hayden), Phoenix,  Arizona,  85012,  United States
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States
Arkansas
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
      Veterans Affairs Medical Center - Little Rock (McClellan), Little Rock,  Arkansas,  72205,  United States
California
      Beckman Research Institute, City of Hope, Duarte,  California,  91010,  United States
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      David Grant Medical Center, Travis Air Force Base,  California,  94535,  United States
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
      University of California Davis Medical Center, Sacramento,  California,  95817,  United States
      USC/Norris Comprehensive Cancer Center, Los Angeles,  California,  90033-0800,  United States
      Veterans Affairs Medical Center - Long Beach, Long Beach,  California,  90822,  United States
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States
Colorado
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Illinois
      CCOP - Central Illinois, Springfield,  Illinois,  62526,  United States
      Loyola University Medical Center, Maywood,  Illinois,  60153,  United States
      Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital), Hines,  Illinois,  60141,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
      University of Kansas Medical Center, Kansas City,  Kansas,  66160-7357,  United States
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States
Kentucky
      Albert B. Chandler Medical Center, University of Kentucky, Lexington,  Kentucky,  40536-0084,  United States
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40511-1093,  United States
Louisiana
      Louisiana State University Hospital - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States
      MBCCOP - LSU Medical Center, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71130,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Veterans Affairs Medical Center - Boston (Jamaica Plain), Jamaica Plain,  Massachusetts,  02130,  United States
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201,  United States
      CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids,  Michigan,  49503,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0752,  United States
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States
Mississippi
      Keesler Medical Center - Keesler AFB, Keesler AFB,  Mississippi,  39534-2576,  United States
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
      Veterans Affairs Medical Center - Biloxi, Biloxi,  Mississippi,  39531-2410,  United States
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      St. Louis University Health Sciences Center, Saint Louis,  Missouri,  63110-0250,  United States
      Veterans Affairs Medical Center - Kansas City, Kansas City,  Missouri,  64128,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
New Mexico
      University of New Mexico Cancer Research & Treatment Center, Albuquerque,  New Mexico,  87131,  United States
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States
New York
      Herbert Irving Comprehensive Cancer Center, New York,  New York,  10032,  United States
      Veterans Affairs Medical Center - Brooklyn, Brooklyn,  New York,  11209,  United States
Ohio
      Barrett Cancer Center, The University Hospital, Cincinnati,  Ohio,  45219,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Cleveland Clinic Cancer Center, Cleveland,  Ohio,  44195,  United States
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428,  United States
Oklahoma
      Oklahoma Medical Research Foundation, Oklahoma City,  Oklahoma,  73104,  United States
      Veterans Affairs Medical Center - Oklahoma City, Oklahoma City,  Oklahoma,  73104,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Texas Tech University Health Science Center, Lubbock,  Texas,  79423,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-1329,  United States
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78284,  United States
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84132,  United States
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Swedish Cancer Institute, Seattle,  Washington,  98104,  United States
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States

Study chairs or principal investigators

Madhav Dhodapkar,  Study Chair,  Southwest Oncology Group   

Study ID Numbers:  CDR0000066431; SWOG-9805
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003416
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08