Clinical Trial: Melphalan, Total-Body Irradiation, and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Previously Untreated Multiple Myeloma

This study is no longer recruiting patients.

Sponsors and Collaborators: National Cancer Institute (NCI)
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Southwest Oncology Group
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy and radiation therapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and radiation therapy and kill more cancer cells. It is not yet known which treatment regimen is more effective for multiple myeloma. PURPOSE: Randomized phase III trial to compare the effectiveness of melphalan, total-body irradiation, and peripheral stem cell transplantation with that of combination chemotherapy in treating patients who have previously untreated multiple myeloma.

Condition Treatment or Intervention Phase
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
 Procedure: chemotherapy
 Procedure: biological response modifier therapy
 Procedure: radiation therapy
 Procedure: autologous bone marrow transplantation
 Procedure: allogeneic bone marrow transplantation
 Procedure: interferon therapy
 Procedure: bone marrow transplantation
 Procedure: peripheral blood stem cell transplantation
 Procedure: cytokine therapy
 Drug: bone marrow ablation with stem cell support
 Drug: carmustine
 Drug: cyclophosphamide
 Drug: dexamethasone
 Drug: doxorubicin
 Drug: interferon alfa
 Drug: melphalan
 Drug: prednisone
 Drug: vincristine
Phase III

MedlinePlus related topics:  Multiple Myeloma

Study Type: Interventional
Study Design: Treatment

Official Title: NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Study of Melphalan/Total Body Irradiation with Peripheral Blood Stem Cell Rescue vs VBMCP (Vincristine/Carmustine/Melphalan/Cyclophosphamide/Prednisone) Following Standard Induction for Previously Untreated Symptomatic Multiple Myeloma, with Further Randomization for Major Responders to Interferon alfa vs Observation

Further Study Details: 

Study start: March 1994

OBJECTIVES: I. Compare tumor cytoreduction achieved with VBMCP (vincristine/carmustine/melphalan/cyclophosphamide/prednisone) vs myeloablative melphalan (L-PAM) and total-body irradiation (TBI) with peripheral blood stem cell (PBSC) rescue in symptomatic myeloma patients with stable or responding disease after induction therapy with VAD (vincristine/doxorubicin/dexamethasone) followed by high dose cyclophosphamide plus filgrastim (G-CSF). II. Compare the efficacy of interferon alfa vs no maintenance therapy in those patients achieving at least 75% cytoreduction to either VBMCP or myeloablative therapy with PBSC rescue. III. Assess allogeneic bone marrow transplantation following the same myeloablative regimen of L-PAM/TBI in patients up to age 55 with an HLA-compatible, MLC-nonreactive donor. (As of 8/1/97, permanent partial closure) IV. Determine whether myeloablative therapy with PBSC rescue can extend the duration of survival by 33% compared to results from standard dose VBMCP. V. Evaluate the toxic effects and possible long term side effects, including development of myelodysplastic disease and/or acute myeloblastic leukemia, associated with these treatments.

PROTOCOL OUTLINE: This is a randomized study. Patients are registered at 5 different points, with stratification occurring at some of these registrations. Registration I: Induction I Registration II: Induction II. Patients are stratified according to stage of disease (I/II vs IIIA vs IIIB), beta-2 microglobulin at diagnosis (less than 6 micrograms/mL vs at least 6 micrograms/mL), and response to Induction I (75-100% regression vs 50-74% regression vs less than 50% regression vs not applicable). Registration III: Patients are randomized to allogeneic bone marrow transplant (BMT) (this arm closed as of 8/1/97) or autologous BMT. Patients are stratified according to treatment received (high dose cyclophosphamide (CTX) and peripheral blood stem cells (PBSC) prior to autologous BMT vs prior to chemotherapy) and beta-2 microglobulin at this registration (less than 2 micrograms/mL vs no greater than 3 micrograms/mL vs unknown). Registration IV: Patients are randomized to maintenance therapy or no further therapy. Those patients who are randomized to maintenance therapy are stratified according to treatment (autologous BMT vs chemotherapy vs chemotherapy followed by autologous BMT) and response to treatment (75-99% regression vs complete response). Registration V: Patients receive autologous BMT as in registration III. Patients are stratified according to prior best response (50% or better vs less than 50% vs not applicable), duration of chemotherapy (at least 6 months vs less than 6 months), and progression after therapy (chemotherapy vs interferon alfa vs observation). Induction I: Patients receive vincristine IV and doxorubicin IV by continuous infusion on days 1-4 and dexamethasone IV or orally on days 1-4, 9-12, and 17-20. Treatment repeats every 5 weeks for up to 4 courses. Patients with progressive disease after 2 courses proceed to PBSC stimulation/harvest. Allogeneic BMT arm is permanently closed as of 8/1/97. Autologous BMT: Therapy begins 4-8 weeks following high dose cyclophosphamide. Patients receive melphalan IV over 1 hour on day -5 and total body irradiation twice a day on days -4 to -1. PBSC are reinfused on day 0. G-CSF SQ is administered beginning on day 1 until blood counts recover. Chemotherapy: Patients receive vincristine IV, carmustine IV, and cyclophosphamide IV on day 1, oral melphalan on days 1-4, and oral prednisone on days 1-7. Treatment repeats every 5 weeks for at least 12 months. Patients who have at least a 75% response to autologous BMT or chemotherapy are randomized to maintenance vs no further therapy. Patients who progress on chemotherapy proceed to autologous BMT (registration V). Maintenance therapy: Therapy begins between 5 and 12 weeks after PBSC rescue. Patients receive interferon alfa SQ three times a week. Treatment continues for 4 years in the absence of disease progression or unacceptable toxicity. Patients who progress on chemotherapy undergo an autologous BMT within 8 weeks after the last course of chemotherapy. Patients who are randomized to receive no further therapy are observed for 1 year.

PROJECTED ACCRUAL: A total of 500 patients will be randomized over about 4 years to autologous transplantation vs chemotherapy as follows: about 250 patients/year will be accrued for induction of whom 200 will achieve at least stable disease, 125 will be randomized, and 15 will have a suitable donor for allogeneic transplant (as of 8/1/97, allogeneic arm of study is closed). Approximately 300 patients are expected to be randomized to maintenance vs no further therapy.

Eligibility

Ages Eligible for Study:  up to  70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Newly diagnosed, active multiple myeloma of any stage requiring treatment

  • Smoldering myeloma (Durie-Salmon stage I) must have a 25% or greater increase in M component levels and/or Bence-Jones protein excretion or development of symptoms

Quantifiable M component of IgG, IgA, IgD, IgE, and/or urinary kappa or lambda light chain (Bence-Jones protein) excretion required

  • Plasmacytosis of at least 30% allowed for non-secretory disease or secretory disease without quantifiable protein
  • IgM peaks excluded

Evaluation of siblings as potential allogeneic bone marrow transplant donors required for patients 55 years of age and younger (As of 8/1/97, permanently closed)

  • HLA followed by DR and MLC testing required

Renal failure, even on dialysis, eligible provided:

  • Cause is attributed to myeloma (Bence-Jones protein or hypercalcemia)
  • Duration does not exceed 2 months

If medically appropriate, the following conditions should be treated prior to registration:

  • Pathologic fractures
  • Pneumonia at diagnosis
  • Hyperviscosity with shortness of breath

--Prior/Concurrent Therapy--

Biologic therapy: Not specified

Chemotherapy: No prior chemotherapy

Endocrine therapy: Not specified

Radiotherapy: No prior radiotherapy except local radiotherapy provided the following cumulative dose limits for prior dose plus potential TBI dose on protocol are not exceeded:

  • Less than 5,000 cGy to bone
  • Less than 4,000 cGy to mediastinum, heart, small bowel, brain, and spinal cord
  • Less than 2,000 cGy to the liver
  • Less than 1,500 cGy to the kidney and lungs

Surgery: Not specified

--Patient Characteristics--

Age: 70 and under

Performance status: SWOG 0-2 (SWOG 3 or 4 based solely on bone pain allowed)

Hematopoietic: Not specified

Hepatic: Not specified

Renal: See Disease Characteristics

Cardiovascular:

  • Normal ejection fraction by ECHO or MUGA
  • No myocardial infarction within 6 months
  • No unstable angina
  • No difficult to control congestive heart failure
  • No uncontrolled hypertension
  • No difficult to control arrhythmias
  • No history of chronic cerebral vascular accident

Pulmonary:

Other:

  • No uncontrolled diabetes
  • No significant comorbid medical condition
  • No uncontrolled, life-threatening infection
  • No prior malignancy within 5 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No prior malignancy treated with cytotoxic drugs used on this protocol
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

Location Information


Arizona
      CCOP - Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States

Colorado
      CCOP - Colorado Cancer Research Program, Inc., Denver,  Colorado,  80209-5031,  United States

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States

Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States

      CCOP - Evanston, Evanston,  Illinois,  60201,  United States

      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States

      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States

      Veterans Affairs Medical Center - Lakeside Chicago, Chicago,  Illinois,  60611,  United States

Indiana
      Indiana University Cancer Center, Indianapolis,  Indiana,  46202-5289,  United States

      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States

Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States

Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States

Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States

Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States

      New England Medical Center Hospital, Boston,  Massachusetts,  02111,  United States

Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States

      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States

Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States

      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States

      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States

      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States

New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States

      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States

      University of Rochester Cancer Center, Rochester,  New York,  14642,  United States

      Veterans Affairs Medical Center - New York, New York,  New York,  10010,  United States

Ohio
      CCOP - Toledo Community Hospital Oncology Program, Toledo,  Ohio,  43623-3456,  United States

      Ireland Cancer Center, Cleveland,  Ohio,  44106-5065,  United States

Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States

      Fox Chase Cancer Center, Philadelphia,  Pennsylvania,  19111,  United States

      Hahnemann University Hospital, Philadelphia,  Pennsylvania,  19102-1192,  United States

      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213-3489,  United States

Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States

      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States

      Veterans Affairs Medical Center - Milwaukee (Zablocki), Milwaukee,  Wisconsin,  53295,  United States

Study chairs or principal investigators

Charles A. Coltman, Jr.,  Study Chair,  Southwest Oncology Group   
Richard L. Schilsky,  Study Chair
Robert A. Kyle,  Study Chair

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

Rajkumar V, Leong T, Fonseca R, et al.: Bone marrow angiogenesis has prognostic value in multiple myeloma: an Eastern Cooperative Oncology Group study. Proceedings of the American Society of Clinical Oncology 18: A68, 19a, 1999.

Study ID Numbers:  CDR0000063310; SWOG-9321; INT-0141
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002548
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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