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

October 19, 2021 updated by: National Heart, Lung, and Blood Institute (NHLBI)

A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy vs Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients With Multiple Myeloma (BMT CTN #0102)

The study is designed as a Phase III, multi-center trial of tandem autologous transplants versus the strategy of autologous followed by Human Leukocyte Antigen (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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

710

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • City of Hope Samaritan
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope National Medical Center
      • La Jolla, California, United States, 92093
        • UCSD Medical Center
      • La Jolla, California, United States, 92037-1027
        • Scripps Clinic/Green Hospital
      • Stanford, California, United States, 94305
        • Stanford Hospital and Clinics
    • Colorado
      • Denver, Colorado, United States, 80218
        • Colorado Blood Cancer Institute
    • Florida
      • Gainesville, Florida, United States, 32610-100277
        • University of Florida College of Medicine (Shands)
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
      • Atlanta, Georgia, United States, 30342
        • BMT Group of Georgia/Northside Hospital
    • Illinois
      • Maywood, Illinois, United States, 60156
        • Loyola University
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health
    • Kansas
      • Wichita, Kansas, United States, 67214
        • Wichita CCOP
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • TUFTS - New England Medical Center
      • Boston, Massachusetts, United States, 02114
        • DFCI/Brigham & Women's
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University of Michigan Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States, 45236
        • Jewish Hospital BMT Program
      • Cleveland, Ohio, United States, 44106
        • University Hospitals of Cleveland/Case Western
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health Sciences University (A)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Cancer Center
      • Philadelphia, Pennsylvania, United States, 19111-2442
        • Fox Chase - Temple University - BMT Program
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
    • Texas
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine/The Methodist Hospital
      • Houston, Texas, United States, 77030
        • University of Texas/MD Anderson Cancer Research Center
      • San Antonio, Texas, United States, 78229
        • Texas Transplant Institute
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Utah BMT/Univ of Utah Med School
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University MCV Hospitals
    • Washington
      • Seattle, Washington, United States, 98109-1024
        • Fred Hutchinson Cancer Research Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792-6164
        • University of Wisconsin Hospitals & Clinics
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 alanine transaminase (ALT) and aspartate transaminase (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: Carbon monoxide diffusion (DLCO), Volume forcibly exhaled in one second (FEV1), and Forced Vital Capacity (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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Auto transplants plus Therapy
One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.
Procedure: One Autologous Transplant
Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.
Procedure: Second Autologous Transplant
Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.
Drug: Thalidomide
Patients will be initiated on a starting dose of 50 mg/day. The dose will be increased weekly by 50 mg as tolerated to achieve a target dose of 200 mg/day. Patients will be treated for 12 months with thalidomide.
Other Names:
  • Thalomid™
Drug: Dexamethasone
Patients will receive dexamethasone at a dose of 40 mg per day during Days 1-4 of each month for 12 months. The first dose of dexamethasone to be given the same day the patient starts thalidomide.
Other Names:
  • Decadron, DexPak
Active Comparator: Auto transplants
One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.
Procedure: One Autologous Transplant
Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.
Procedure: Second Autologous Transplant
Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.
Behavioral: Observation
One year of observation post-transplants.
Active Comparator: Auto and Allo transplants
One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.
Procedure: One Autologous Transplant
Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.
Behavioral: Observation
One year of observation post-transplants.
Procedure: Non-Myeloablative Allogeneic Transplant
Upon recovery and at least Day 60 post-autograft, patients with an available 6/6 HLA matched sibling will receive an allograft after non-myeloablative conditioning. Day 0 patients will receive Total Body Irradiation (TBI) 2.0 Gy from a linear accelerator ≤ 20 cGy/min, followed by allogeneic peripheral blood stem cell (PBSC) infusion. Commence cyclosporine (CSA) on Day -3 at 5 mg/kg bid PO for a daily dose of 10 mg/kg/day through Day +84 based on actual body weight. Starting on Day 84, patients in partial or complete response with the absence of graph versus host disease (GVHD) will have CSA tapered so the patient will be off CSA by Day 180. Oral administration of Mycophenolate Mofetil will be at a daily dose of 30 mg/kg/day from the evening of Day 0 until Day 27 post-transplant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: Year 3
Patients are considered a failure for this endpoint if they die or if they progress or relapse.
Year 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS) for Standard Risk
Time Frame: Years 1, 2, and 3
The event is death from any cause, patients alive at the time of last observation are considered censored.
Years 1, 2, and 3
Overall Survival (OS) for High Risk
Time Frame: Year 3
The event is death from any cause, patients alive at the time of last observation are considered censored.
Year 3
Cumulative Incidence of Progression/Relapse
Time Frame: Year 3
Patients are considered experiencing an event when they progress. Deaths without progression are considered as a competing risk. Patients initiating non-protocol anti-myeloma therapy are considered to have progressed on this protocol.
Year 3
Cumulative Incidence of Treatment Related Mortality (TRM)
Time Frame: Year 3
TRM is defined as death occurring in a patient from causes other than relapse or progression.
Year 3
Interval From First to Second Transplantation
Time Frame: Year 1
Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients will receive a second transplant according to treatment assignments.
Year 1
Incidences of Graft Versus Host Disease (GVHD)
Time Frame: Day 100
Incidence and severity of GVHD will be scored according to the BMT clinical trials network Manual of Procedures.
Day 100
Incidences of Chronic GVHD
Time Frame: Years 1 and 2
Incidence and severity of chronic GVHD will be scored according to the BMT clinical trials network Manual of Procedures.
Years 1 and 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborators

National Cancer Institute (NCI)
National Marrow Donor Program
Blood and Marrow Transplant Clinical Trials Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

June 1, 2012

Study Completion (Actual)

March 1, 2013

Study Registration Dates

First Submitted

January 9, 2004

First Submitted That Met QC Criteria

January 12, 2004

First Posted (Estimate)

January 13, 2004

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 19, 2021

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMTCTN0102
  • 417 (NHLBI)
  • BMT CTN 0102 (Other Identifier: Blood and Marrow Transplant Clinicial Trials Network)
  • SUMC-79730 (Other Identifier: Institutional Review Board at SUMC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

IPD Sharing Time Frame

Within 6 months of official study closure at participating sites.

IPD Sharing Access Criteria

Available to the public

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: BMT CTN-0102
    Information comments: NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local Institutional Review Board (IRB) approval or certification of exemption from IRB review, and completion of a data use agreement.
  2. Study Protocol
    Information identifier: BMT CTN-0102
  3. Study Forms
    Information identifier: BMT CTN-0102

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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