Stem Cell Transplantation in Individuals With Multiple Myeloma (BMT CTN 0102)

This study has been completed.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00075829
First received: January 9, 2004
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

The study is designed as a Phase III, multi-center trial of tandem autologous transplants versus the strategy of autologous followed by HLA-matched sibling non-myeloablative allogeneic transplant. Study subjects will be biologically assigned to the appropriate arm depending on the availability of an HLA-matched sibling. There is a nested randomized phase III trial of observation versus maintenance therapy following the second autologous transplant for patients on the tandem autologous transplant arm.


Condition Intervention Phase
Multiple Myeloma
Procedure: Tandem Autologous Transplant
Drug: Autologous Transplant Plus Non-Myeloablative Allogeneic Transplant
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy Versus Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients With Multiple Myeloma (BMT CTN #0102)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Three-year progression-free survival [ Time Frame: Measured at 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Current myeloma-stable survival [ Time Frame: Measured at 3 years ] [ Designated as safety issue: Yes ]
  • Three-year overall survival [ Time Frame: Measured at 3 years ] [ Designated as safety issue: Yes ]
  • Incidence of progression [ Time Frame: Measured at 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 710
Study Start Date: December 2003
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Autologous transplant plus dexamethasone/thalidomide
Procedure: Tandem Autologous Transplant
Transplant plus dexamethasone/thalidomide
Active Comparator: 2
Autologous transplant plus observation
Drug: Autologous Transplant Plus Non-Myeloablative Allogeneic Transplant
Transplant
Active Comparator: 3
Autologous transplant plus allogeneic transplant plus observation
Drug: Autologous Transplant Plus Non-Myeloablative Allogeneic Transplant
Transplant

Detailed Description:

Multiple myeloma (MM), characterized by malignant plasma cell proliferation, bone destruction, and immunodeficiency, is a disease with a median age at diagnosis of approximately 65 years. It is responsible for about 1 percent of all cancer-related deaths in Western Countries. Conventional treatments with chemotherapy and radiation therapy are non-curative but improve quality of life and duration of survival. Attempts to cure myeloma through high-dose therapy followed by autografting or allografting have largely failed due to a combination of relapsed disease or transplant related mortality (TRM). High-dose therapy with autologous transplantation is safe and has low TRM (less than 5%), but is associated with a continuing and nearly universal risk of disease progression and relapse. Even so, autologous transplantation is superior to continued conventional chemotherapy. Recent data indicate that tandem autologous transplants are superior to a single procedure. Even with this approach, patients remain at risk of relapse and additional approaches are needed.

DESIGN NARRATIVE:

The overall study design is that of biologic assignment, based on the availability of an HLA-matched sibling, to one of two treatment strategies for MM patients. Patients without an HLA-matched sibling will undergo tandem autologous transplants. Patients with an HLA-matched sibling will undergo an autologous transplant followed by a non-myeloablative allogeneic transplant. In addition, the tandem autologous transplant recipients will be randomized to either observation or one year of maintenance therapy to begin following the second autologous transplant. The large number of MM patients without an HLA-matched sibling enables us to evaluate the role of maintenance therapy following tandem autologous transplants.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meeting the Durie and Salmon criteria for initial diagnosis of MM
  • Stage II or III MM at diagnosis or anytime thereafter
  • Symptomatic MM requiring treatment at diagnosis or anytime thereafter
  • Received at least three cycles of initial systemic therapy and are within 2-10 months of initiation of the initial therapy (this time frame excludes the time for mobilization therapy)
  • If receiving chemotherapy-based mobilization regimens, must be able to receive high-dose melphalan between 2 and 8 weeks after the initiation of mobilization therapy whether delivered at the transplant center or at a referring center
  • Adequate organ function as measured by:

    1. Cardiac: Left ventricular ejection fraction at rest greater than 40%
    2. Hepatic: Bilirubin less than 2 times the upper limit of normal and ALT and AST less than 3 times the upper limit of normal
    3. Renal: Creatinine clearance greater than 40 ml/min (measured or calculated/estimated)
    4. Pulmonary: DLCO, FEV1, and FVC greater than 50% of predicted value (corrected for hemoglobin), or O2 saturation greater than 92% of room air
  • An adequate autologous graft defined as a cryopreserved PBSC graft containing at least 4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known that a patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched sibling donor is available), the required autograft must contain at least 2.0 x 10^6 CD34+ cells/kg patient weight; the graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells; the graft can be collected at the transplanting institution or by a referring center; for patients without an HLA-matched sibling donor, the autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight

Exclusion Criteria:

  • Never advanced beyond Stage I MM since diagnosis
  • Non-secretory MM (absence of a monoclonal protein [M protein] in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques)
  • Plasma cell leukemia
  • Karnofsky performance score less than 70%, unless approved by the Medical Monitor or one of the Protocol Chairs
  • Uncontrolled hypertension
  • Uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms)
  • Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or one of the Protocol Chairs; cancer treated with curative intent more than 5 years previously will be allowed
  • Pregnant or breastfeeding
  • Seropositive for the human immunodeficiency virus (HIV)
  • Unwilling to use contraceptive techniques during and for 12 months following treatment
  • Prior allograft or prior autograft
  • Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy
  • Prior organ transplant requiring immunosuppressive therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075829

  Show 39 Study Locations
Sponsors and Collaborators
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Chair: David G. Maloney, MD, PhD Fred Hutchinson Cancer Research Center
Study Chair: Amrita Y. Krishnan, MD Beckman Research Institute
Principal Investigator: Donna Salzman, MD University of Alabama at Birmingham
Principal Investigator: Jeffrey Schriber, MD City of Hope Samaritan
Principal Investigator: James Mason, MD Scripps Clinic/Green Hospital
Principal Investigator: Keith Goldstein, MD Stanford Hospital and Clinics
Principal Investigator: Edward Ball, MD UCSD Medical Center
Principal Investigator: Michael Maris, MD Rocky Mountain BMT
Principal Investigator: John Wingard, MD University of Florida College of Medicine (Shands)
Principal Investigator: Lawrence Morris, MD BMT Group of Georgia/Northside Hospital
Principal Investigator: Melvin Moore, MD DeKalb Medical Center
Principal Investigator: Amir Toor, MD Loyola University
Principal Investigator: James Thompson, MD Indiana BMT at Beech Grove
Principal Investigator: Shaker Dakhil, MD Wichita CCOP
Principal Investigator: Thomas Spitzer, MD DFCI/Brigham & Women's
Principal Investigator: Hans-Georg Klingemann, MD, PhD Tufts Medical Center
Principal Investigator: Choon-Kee Lee, MD University of Michigan
Principal Investigator: Daniel Weisdorf, MD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Joseph McGuirk, MD Kansas City Cancer Centers
Principal Investigator: John DiPersio, MD, PhD Washington University/Banres Jewish Hospital
Principal Investigator: Nelson Chao, MD Duke University
Principal Investigator: Marcel Devetten, MD University of Nebraska
Principal Investigator: Scott Rowely, MD Hackensack Universiy Medical Center
Principal Investigator: Raymond Comenzo, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Brian Bolwell, MD The Cleveland Clinic
Principal Investigator: Hillard Lazarus, MD University Hospitals of Cleveland/Case Western
Principal Investigator: George Selby, MD University of Oklahoma Medical Center
Principal Investigator: Richard Maziarz, MD Oregon Health Sciences University (A)
Principal Investigator: Robert Emmon Fox Chase - Temple University - BMT Program
Principal Investigator: Edward Stadtmauer, MD University of Pennsylvania
Principal Investigator: Stacey Goodman, MD Vanderbilt University
Principal Investigator: Robert Collins, MD University of Texas Southwestern Medical Center
Principal Investigator: George Currum, MD Baylor College of Medicine/The Methodist Hospital
Principal Investigator: Brian Berryman, MD Baylor Health Care System
Principal Investigator: Paul Shaughnessy, MD Texas Transplant Institute
Principal Investigator: Sergio Giralt, MD University of Texas/MD Anderson Cancer Research Center
Principal Investigator: John McCarty, MD Virginia Commonwealth University MCV Hospitals
Principal Investigator: J. Douglas Rizzo, MD Medical College of Wisconsin
Principal Investigator: Mark Juckett, MD University of Wisconsin Hospital & Clinics
  More Information

Additional Information:
Publications:
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT00075829     History of Changes
Obsolete Identifiers: NCT00321607, NCT00386568
Other Study ID Numbers: 417, BMTCTN-0102, SUMC-79730, SWOG-BMTCTN-0102, CDR0000349416
Study First Received: January 9, 2004
Last Updated: October 31, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Refractory Plasma Cell Neoplasm

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014