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

• ClinicalTrials.gov Identifier: NCT00075829
• Recruitment Status: Completed
• First Posted: January 13, 2004
• Results First Posted: August 4, 2016
• Last Update Posted: November 1, 2021
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: Blood and Marrow Transplant Clinical Trials Network; National Cancer Institute (NCI); National Marrow Donor Program
• Information provided by (Responsible Party): National Heart, Lung, and Blood Institute (NHLBI)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Procedure: One Autologous Transplant; Procedure: Non-Myeloablative Allogeneic Transplant; Procedure: Second Autologous Transplant; Drug: Thalidomide; Drug: Dexamethasone; Behavioral: Observation	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 710 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: December 2003
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: March 2013

Arms and Interventions

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 Name: 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 Name: 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.; 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.; Behavioral: Observation; One year of observation post-transplants.

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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.
2. 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.
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.
4. 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.
5. 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.
6. 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.
7. 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.

Eligibility Criteria

• Ages Eligible for Study: up to 70 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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 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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Arizona

City of Hope Samaritan

Phoenix, Arizona, United States, 85006

United States, California

City of Hope National Medical Center

Duarte, California, United States, 91010-3000

Scripps Clinic/Green Hospital

La Jolla, California, United States, 92037-1027

UCSD Medical Center

La Jolla, California, United States, 92093

Stanford Hospital and Clinics

Stanford, California, United States, 94305

United States, Colorado

Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

United States, Florida

University of Florida College of Medicine (Shands)

Gainesville, Florida, United States, 32610-100277

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

BMT Group of Georgia/Northside Hospital

Atlanta, Georgia, United States, 30342

United States, Illinois

Loyola University

Maywood, Illinois, United States, 60156

United States, Indiana

IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health

Indianapolis, Indiana, United States, 46237

United States, Kansas

Wichita CCOP

Wichita, Kansas, United States, 67214

United States, Massachusetts

Tufts - New England Medical Center

Boston, Massachusetts, United States, 02111

DFCI/Brigham & Women's

Boston, Massachusetts, United States, 02114

United States, Michigan

University of Michigan Medical Center

Ann Arbor, Michigan, United States, 48109-0942

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Nebraska

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10021

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Jewish Hospital BMT Program

Cincinnati, Ohio, United States, 45236

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, United States, 44106

United States, Oklahoma

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Oregon Health Sciences University (A)

Portland, Oregon, United States, 97239-3098

United States, Pennsylvania

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States, 19104

Fox Chase - Temple University - BMT Program

Philadelphia, Pennsylvania, United States, 19111-2442

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37232

United States, Texas

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, United States, 77030

University of Texas/MD Anderson Cancer Research Center

Houston, Texas, United States, 77030

Texas Transplant Institute

San Antonio, Texas, United States, 78229

United States, Utah

Utah BMT/Univ of Utah Med School

Salt Lake City, Utah, United States, 84132

United States, Virginia

Virginia Commonwealth University MCV Hospitals

Richmond, Virginia, United States, 23298

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109-1024

United States, Wisconsin

University of Wisconsin Hospitals & Clinics

Madison, Wisconsin, United States, 53792-6164

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network

National Cancer Institute (NCI)

National Marrow Donor Program

Investigators

• Study Director: Mary Horowitz, MD; Center for International Blood and Marrow Transplant Research

  Study Documents (Full-Text)

Documents provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] May 15, 2006

More Information

Additional Information:

Blood and Marrow Transplant Clinical Trials Network Website 

National Marrow Donor Program 

Study Data/Documents: Individual Participant Data Set 

Identifier: BMT CTN-0102
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.

Study Protocol 

Identifier: BMT CTN-0102

Study Forms 

Identifier: BMT CTN-0102

Publications of Results:

Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; Blood Marrow Transplant Clinical Trials Network (BMT CTN). Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. doi: 10.1016/S1470-2045(11)70243-1. Epub 2011 Sep 29.

Logan B, Leifer E, Bredeson C, Horowitz M, Ewell M, Carter S, Geller N. Use of biological assignment in hematopoietic stem cell transplantation clinical trials. Clin Trials. 2008;5(6):607-16. doi: 10.1177/1740774508098326.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Giralt S, Costa LJ, Maloney D, Krishnan A, Fei M, Antin JH, Brunstein C, Geller N, Goodman S, Hari P, Logan B, Lowsky R, Qazilbash MH, Sahebi F, Somlo G, Rowley S, Vogl DT, Vesole DH, Pasquini M, Stadtmauer E. Tandem Autologous-Autologous versus Autologous-Allogeneic Hematopoietic Stem Cell Transplant for Patients with Multiple Myeloma: Long-Term Follow-Up Results from the Blood and Marrow Transplant Clinical Trials Network 0102 Trial. Biol Blood Marrow Transplant. 2020 Apr;26(4):798-804. doi: 10.1016/j.bbmt.2019.11.018. Epub 2019 Nov 19.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00075829
• Obsolete Identifiers: NCT00321607, NCT00386568
• Other Study ID Numbers: BMTCTN0102; BMT CTN 0102 ( Other Identifier: Blood and Marrow Transplant Clinicial Trials Network ); SUMC-79730 ( Other Identifier: Institutional Review Board at SUMC ); 417 ( Other Identifier: NHLBI )
• First Posted: January 13, 2004
• Results First Posted: August 4, 2016
• Last Update Posted: November 1, 2021
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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).
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public
• URL: https://biolincc.nhlbi.nih.gov/home/

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; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Thalidomide; Dexamethasone; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Leprostatic Agents