Clinical Trial: Tandem Autologous Stem Cell Transplantation With or Without Maintenance Therapy After the Second Transplantation Compared With Autologous Stem Cell Transplantation Followed By Matched Sibling Allogeneic Stem Cell Transplantation in Patients With Stage II

This study is currently recruiting patients.

Sponsors and Collaborators: Blood and Marrow Transplant Clinical Trials Network
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Southwest Oncology Group
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant, using stem cells from the patient or a brother or sister, may allow more chemotherapy to be given so more cancer cells are killed. Giving maintenance therapy after a stem cell transplant may kill any cancer cells that remain. Sometimes the transplanted cells can be rejected by the body's tissues. Cyclosporine, total-body irradiation, and mycophenolate mofetil may prevent this. It is not yet known whether an autologous stem cell transplant followed by maintenance therapy is more effective than an autologous stem cell transplant followed by an allogeneic stem cell transplant in treating multiple myeloma.

PURPOSE: This randomized phase III trial is studying to compare the effectiveness of tandem (two) autologous stem cell transplantation with or without maintenance therapy with that of autologous stem cell transplantation followed by matched sibling (brother or sister) allogeneic (donor) stem cell transplantation in treating patients who have stage II or stage III multiple myeloma.

Condition Treatment or Intervention Phase
stage II multiple myeloma
stage III multiple myeloma
refractory plasma cell neoplasm
 Drug: cyclosporine
 Drug: dexamethasone
 Drug: filgrastim
 Drug: melphalan
 Drug: mycophenolate mofetil
 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: endocrine therapy
 Procedure: graft versus host disease prophylaxis/therapy
 Procedure: graft versus tumor induction
 Procedure: growth factor antagonist therapy
 Procedure: high-dose chemotherapy
 Procedure: hormone therapy
 Procedure: non-specific immune-modulator therapy
 Procedure: peripheral blood stem cell transplantation
 Procedure: radiation therapy
 Procedure: steroid therapy
 Procedure: supportive care/therapy
Phase III

MedlinePlus related topics:  Immune System and Disorders;   Lymphatic Diseases;   Multiple Myeloma

Study Type: Interventional
Study Design: Treatment

Official Title: Phase III Randomized Study of Tandem Autologous Stem Cell Transplantation With or Without Maintenance Therapy After the Second Transplantation Versus Single Autologous Stem Cell Transplantation Followed By Matched Sibling Nonmyeloablative Allogeneic Stem Cell Transplantation in Patients With Stage II or III Multiple Myeloma

Further Study Details: 

OBJECTIVES: Primary

Secondary

  • Compare "current" myeloma-stable survival and 3-year overall survival of patients treated with these regimens.
  • Compare the incidence of progression in patients treated with these regimens.

Tertiary

OUTLINE: This is a multicenter study with a randomized portion. Patients are stratified according to disease risk status (high vs standard) and participating center.

All patients receive an initial autologous stem cell transplantation (SCT).

  • Conditioning for autologous SCT: Patients receive high-dose melphalan IV over 15-20 minutes on day -2.
  • Autologous SCT: Patients receive autologous SCT on day 0. Patients also receive filgrastim (G-CSF) subcutaneously or IV daily beginning on day 5 and continuing until blood counts recover. Upon recovery from the initial autologous SCT (between 60-120 days), patients with an HLA-matched sibling donor receive an allogeneic SCT with nonmyeloablative conditioning. Patients without an HLA-matched sibling donor receive a second autologous SCT with conditioning as above.
  • Nonmyeloablative conditioning for allogeneic SCT: Patients undergo total body irradiation (TBI) on day 0.
  • Allogeneic transplantation: Patients receive allogeneic SCT on day 0 after the completion of TBI.
  • Immunosuppression: Patients receive oral or IV cyclosporine twice daily beginning on day -3 followed by a taper beginning on day 84 and continuing until day 114 if disease is not in complete remission (CR) or partial remission (PR) on day 84 OR until day 180 if disease is in CR or PR on day 84. Patients also receive oral mycophenolate mofetil twice daily OR IV 3 times daily on days 0-27. Patients receiving a second autologous SCT are randomized to 1 of 2 treatment arms for maintenance therapy or observation beginning at least 60 days after the second transplantation.
  • Arm I: Patients receive oral thalidomide daily beginning on day 1 and oral dexamethasone on days 1-4. Courses repeat monthly for 12 months in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo observation. Quality of life is assessed at baseline, before the second transplantation, at 6 months, 1 year, and then annually for 2 years post-transplantation.

Patients receiving an allogeneic SCT are followed weekly for approximately 14 weeks, at 6 months, and then every 6 months for 2.5 years post-transplantation.

Patients receiving tandem autologous SCTs are followed weekly for approximately 14 weeks, monthly for 6 months, and then every 6 months for 2.5 years post-transplantation.

PROJECTED ACCRUAL: A total of 450-750 patients, including 150 standard-risk patients assigned to the autologous/allogeneic arm, will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:  up to  70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of multiple myeloma meeting the Durie and Salmon criteria
  • Stage II or III disease
  • Symptomatic disease requiring treatment
  • Previously treated with at least 3 months of systemic therapy with no more than 2-9 months since the initiation of that therapy, excluding the time for mobilization chemotherapy
  • Adequate autologous graft defined as a cryopreserved peripheral blood stem cell graft containing ≥ 4.0 x 10
  • CD34+ cells/kg*
  • No graft CD34+ selected or otherwise manipulated to remove tumor or other cells
  • Patients without an HLA-matched sibling donor must have 2 products, each containing ≥ 2 x 10^6 CD34+ cells/kg NOTE: *Patients with an identified HLA-matched sibling must have ≥ 2.0 x 106 CD34+ cells/kg
  • No non-secretory multiple myeloma (i.e., absence of Bence Jones protein in the urine by conventional electrophoresis and immunofixation techniques)
  • No plasma cell leukemia
  • 6/6 HLA genotypically identical sibling donor (for patients receiving allogeneic stem cell transplantation [SCT])
  • No identical twin

PATIENT CHARACTERISTICS: Age

  • 70 and under

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin < 2 times upper limit of normal (ULN)
  • ALT and AST < 3 times ULN

Renal

  • Creatinine clearance > 40 mL/min

Cardiovascular

  • LVEF > 40% at rest
  • No uncontrolled hypertension

Pulmonary

  • DLCO > 50% of predicted*
  • FEV_1 > 50% of predicted*
  • FVC > 50% of predicted* NOTE: *Corrected for hemoglobin

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after study participation
  • HIV negative
  • No uncontrolled bacterial, viral, or fungal infection (i.e., currently treating with medication with progression of clinical symptoms)
  • No other malignancy within the past 5 years except resected basal cell carcinoma or treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

  • No prior autograft or allograft

Chemotherapy

  • See Disease Characteristics
  • No prior mid-intensity melphalan (> 50 mg IV)

Endocrine therapy

  • Not specified

Radiotherapy

  • No concurrent radiotherapy during melphalan administration
  • Concurrent radiotherapy allowed for the following reasons provided patient is recovered from autologous SCT:
  • Palliation of pain from bone lesions
  • Prevention of pathologic fractures
  • Relief of spinal cord compression or nerve root compression

Surgery

  • Not specified

Location and Contact Information


Arizona
      Banner Good Samaritan Medical Center, Phoenix,  Arizona,  85006,  United States; Recruiting
Jeffrey Schriber, MD  602-239-4526    jeffrey.schriber@bannerhealth.com 

California
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
Clinical Trials Office - New Patient Services  800-826-4673    becomingapatient@coh.org 

      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92037-0960,  United States; Recruiting
Edward D. Ball, MD  858-657-7058 

      Scripps Cancer Center at Scripps Clinic, La Jolla,  California,  92037-1027,  United States; Recruiting
James Ronald Mason, MD  858-554-8597 

      Stanford Cancer Center at Stanford University Medical Center, Stanford,  California,  94305-5623,  United States; Recruiting
Keith E. Stockert-Goldstein, MD  650-723-0822    ksgold@stanford.edu 

Florida
      University of Florida Shands Cancer Center, Gainesville,  Florida,  32610-100277,  United States; Recruiting
John Reid Wingard, MD  352-846-1846    wingajr@medicine.ufl.edu 

Georgia
      Blood and Marrow Transplant Group of Georgia, Atlanta,  Georgia,  30342-4777,  United States; Recruiting
Lawrence E. Morris, MD  404-255-1930    lmorris@bmtga.com 

      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States; Recruiting
Sagar Lonial, MD  404-727-5572 

Indiana
      Indiana Blood and Marrow Transplantation, Beech Grove,  Indiana,  46107,  United States; Recruiting
James M. Thompson, DO  317-865-5500    jthompson@ibmtindy.com 

Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
Edwin P. Alyea, MD  617-632-3903    epalyea@bics.bwh.harvard.edu 

Michigan
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0942,  United States; Recruiting
Christopher Reynolds, MD  734-936-8788 

Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
Daniel J. Weisdorf, MD  612-624-3101 

Missouri
      Kansas City Cancer Centers - Central, Kansas City,  Missouri,  64111,  United States; Recruiting
Joseph McGuirk, DO  816-531-2740 

      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
Steven M. Devine, MD  314-935-5000 

Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Stefano R. Tarantolo, MD  402-559-5520    staranto@unmc.edu 

New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
Scott D. Rowley, MD, FACP  201-996-5900 

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
Hugo R. Castro-Malaspina, MD  212-639-8197 

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
Nelson J. A. Chao, MD  919-668-1011    chao0002@mc.duke.edu 

Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
Brian James Bolwell, MD  216-444-6922 

      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Hillard M. Lazarus, MD  216-844-1000    hml@po.cwru.edu 

Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Richard Maziarz, MD  503-494-1551    maziarzr@ohsu.edu 

Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
Edward Allen Stadtmauer, MD  215-662-7910    edward.stadtmauer@uphs.upenn.edu 

      Fox Chase/Temple University BMT Program, Philadelphia,  Pennsylvania,  19111-2442,  United States; Recruiting
Anand Jillella, MD  215-214-3129    jillelap@tuhs.temple.edu 

Tennessee
      Veterans Affairs Medical Center - Tennessee Valley Healthcare System - Nashville Campus, Nashville,  Tennessee,  37212,  United States; Recruiting
Stacey Goodman, MD  615-321-6373    stacey.goodman@med.va.gov 

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting
Sergio Giralt, MD  713-794-5745    sgiralt@mail.mdanderson.org 

      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75235-8590,  United States; Recruiting
Robert H. Collins, MD  214-648-4155    robert.collins@utsouthwestern.edu 

      Texas Transplant Institute, San Antonio,  Texas,  78229,  United States; Recruiting
Paul Shaughnessy, MD  210-575-8500    paul.shaughnessy@mhshealth.com 

Utah
      Huntsman Cancer Institute at University of Utah, Salt Lake City,  Utah,  84112,  United States; Recruiting
Michael A. Pulsipher, MD  801-588-3498    michael.pulsipher@hsc.utah.edu 

Virginia
      Massey Cancer Center at Virginia Commonwealth University, Richmond,  Virginia,  23298-0037,  United States; Recruiting
John M. McCarty, MD  804-828-4360    jmccarty@hsc.vcu.edu 

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting
David G. Maloney, MD, PhD  206-667-5616    dmaloney@fhcrc.org 

Wisconsin
      Medical College of Wisconsin Cancer Center, Milwaukee,  Wisconsin,  53226,  United States; Recruiting
James Douglas Rizzo  414-456-8325    rizzo@mcw.edu 

      University of Wisconsin Comprehensive Cancer Center, Madison,  Wisconsin,  53792,  United States; Recruiting
Mark B. Juckett, MD  608-263-1836    mbj@medicine.wisc.edu 

Study chairs or principal investigators

David G. Maloney, MD, PhD,  Study Chair,  Fred Hutchinson Cancer Research Center   
Firoozeh Sahebi, MD,  Beckman Research Institute   
David G. Maloney, MD, PhD,  Study Chair,  Fred Hutchinson Cancer Research Center   

More Information

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

Study ID Numbers:  CDR0000349416; BMTCTN-0102; SUMC-79730; SWOG-BMTCTN-0102; NCT00075829
Record last reviewed:  November 2004
Last Updated:  April 4, 2005
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075829
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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