Peripheral Blood Stem Cell Transplant vs Bone Marrow Transplant in Individuals With Hematologic Cancers (BMT CTN 0201)

December 7, 2022 updated by: Medical College of Wisconsin

A Phase III Randomized, Multicenter Trial Comparing G-CSF Mobilized Peripheral Blood Stem Cell With Marrow Transplantation From Human Leukocyte Antigen (HLA) Compatible Unrelated Donors (BMT CTN #0201)

The study is designed as a Phase III, randomized, open label, multicenter, prospective, comparative trial of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) versus marrow from unrelated donors for transplantation in patients with hematologic malignancies. Recipients will be stratified by transplant center and disease risk and will be randomized to either the PBSC or marrow arm in a 1:1 ratio.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

BACKGROUND:

Many studies of allogeneic marrow transplantation have shown that a higher dose of marrow cells correlates with more robust hematopoietic engraftment and lower mortality from infectious complications. Peripheral blood stem cells (PBSC) collected after mobilization with granulocyte colony stimulating factor (G-CSF) contain a larger number of CD34-positive (CD34) progenitors and total cells than bone marrow. These observations led to the hypothesis that transplantation of PBSC would lead to lower mortality compared to transplantation of marrow. In addition, PBSC grafts have a higher T cell content, predicting a possibly more powerful anti-leukemia effect. However, the higher T cell content of PBSC may also lead to increased incidence and severity of acute and chronic graft-versus-host disease (GVHD). This concern is especially serious when the donor is unrelated to the recipient. This prospective, randomized, multicenter clinical trial of unrelated donor transplantation will test the hypothesis that transplantation of PBSC leads to similar patient survival compared to transplantation of marrow.

DESIGN NARRATIVE:

This is a Phase III randomized, open label, multicenter clinical trial sponsored by the National Marrow Donor Program (NMDP) and the National Institutes of Health (NIH). The objective of the trial is to test the null hypothesis that there is no difference in overall survival after PBSC versus marrow transplants from HLA compatible unrelated donors. The study will compare G-CSF-mobilized PBSC transplantation with bone marrow transplantation from HLA-compatible unrelated donors for patients with leukemia, myelodysplastic or myeloproliferative syndromes. Conditioning and GVHD prophylaxis regimens will vary by center and within centers, however, the center must declare before randomization what regimens will be used for each patient. The primary endpoint of this trial is 2-year survival following randomization. Secondary analyses will consider neutrophil and platelet recovery, acute and chronic GVHD, time off all immunosuppressive therapy, relapse, infections, adverse events and immune reconstitution. The trial will include evaluation of patient and donor quality of life, composition of the graft, and immune reconstitution. Accrual is anticipated for 3 years with a follow-up period of 3 years.

Study Type

Interventional

Enrollment (Actual)

551

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

  • Canada
      • Halifax, Canada
        • Queen Elizabeth II Health Sciences Centre - Halifax
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre, Calgary
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z1M9
        • Vancouver General Hospital
    • Ontario
      • Hamilton, Ontario, Canada
        • Hamilton Health Sciences - McMaster Site
      • Ottawa, Ontario, Canada
        • Ottawa Hospital
      • Toronto, Ontario, Canada, M5G 2M9
        • University of Toronto, Princess Margaret Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • La Jolla, California, United States, 92093-0960
        • UCSD Cancer Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
      • Stanford, California, United States, 94305
        • Stanford Hospital and Clinics
    • Florida
      • Gainesville, Florida, United States, 32610-100277
        • University of Florida College of Medicine (Shands)
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa hospitals and Clinics
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21228
        • University of Maryland
    • Massachusetts
      • 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
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University/St. Louis Children's Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University/Barnes Jewish Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198-3330
        • University of Nebraska Medical Center
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • New Hyde Park, New York, United States, 11040
        • Cohen Children's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medical Center
      • Winston-Salem, North Carolina, United States, 27157-1082
        • Wake Forest University Health Sciences
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State/Arthur G. James Cancer Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health Sciences University
      • Portland, Oregon, United States, 97239-3098
        • Oregon Health & Science University (Peds)
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt University
    • Texas
      • Dallas, Texas, United States, 77030
        • Baylor University Medical Center
      • Houston, Texas, United States, 77030-2399
        • Baylor College of Medicine/The Methodist Hospital
      • Houston, Texas, United States, 77030-4009
        • University of Texas/MD Anderson CRC
      • San Antonio, Texas, United States, 78229
        • Texas Transplant Institute
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Utah BMT/Primary Children's Medical Center
      • Salt Lake City, Utah, United States, 84132
        • Utah BMT/University of Utah Medical School
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Virginia Commonwealth University MCV Hospitals
    • Washington
      • Seattle, Washington, United States, 98104
        • Fred Hutchinson Cancer Research Center

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 66 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Patient Inclusion Criteria:

One of the following diagnoses:

  • Acute myelogenous leukemia at the following stages: first remission, second remission, third or subsequent remission, or not in remission
  • Acute lymphoblastic leukemia at the following stages: first remission, second remission, third or subsequent remission, or not in remission
  • Chronic myelogenous leukemia at the following stages: chronic phase, accelerated phase, or blast phase
  • Myelodysplastic syndromes (MDS) at the following stages: refractory anemia; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; refractory cytopenia with multilineage dysplasia and ringed sideroblasts; refractory anemia with excess blasts-1 (5-10% blasts); refractory anemia with excess blasts-2 (10-20% blasts); myelodysplastic syndrome, unclassified; or MDS associated with isolated del (5q)
  • Myeloproliferative diseases: chronic myelomonocytic leukemia; agnogenic myeloid metaplasia with myelofibrosis (idiopathic myelofibrosis); juvenile myelomonocytic leukemia
  • Therapy-related acute myelogenous leukemia (AML) or MDS with prior malignancy that has been in remission for at least 12 months. If the remission is less than 12 months, Medical Monitor or Protocol Chair approval is required for eligibility

Patient Exclusion Criteria:

  • Prior allogeneic or autologous transplants using any hematopoietic stem cell source; patients with secondary malignancies who have had a prior autologous transplant will be eligible; the prior autologous transplant must have been performed for the primary malignancy (such as lymphoma) and must have occurred 12 or more months prior to enrollment
  • Lymphoma (11% of 2001 NMDP transplants), other malignant disorders (6%), and non-malignant disorders (9%)

Donor Inclusion Criteria:

  • Matched for HLA-A, B, and DRB1 antigens

    1. One antigen mismatch at HLA-A, B, or DRB1 is acceptable with or without mismatch at HLA-C
    2. Typing is by DNA techniques: intermediate resolution for A, B, and C, and high resolution for DRB1. HLA-C typing is mandatory but will not count in the match.
  • Willing to undergo both bone marrow harvest and G-CSF administration with apheresis
  • Willing to be randomly assigned to either marrow or PBSC collection
  • Adequate peripheral venous access for leukapheresis or willing to undergo placement of a central catheter
  • Donor center affiliation with NMDP
  • Additional donor inclusion criteria can be found in the Donor Companion Manual

Donor Exclusion Criteria:

  • Pregnant (positive serum β-HCG) or uninterruptible breastfeeding
  • Known allergy to G-CSF or to E. Coli-derived recombinant protein products
  • History of autoimmune disorders
  • History of deep vein thrombosis or venous thromboembolism
  • History of iritis or episcleritis
  • History of serious adverse reaction to anesthesia
  • Thrombocytopenia (platelets less than 150,000 per mcL) at baseline evaluation
  • Current treatment with lithium
  • Presence of sickle hemoglobin as demonstrated by appropriate testing such as hemoglobin electrophoresis
  • Receiving experimental therapy or investigational agents

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Bone Marrow Transplant
Allogeneic bone marrow transplantation
Biological: Allogeneic bone marrow transplantation
Bone marrow transplant from HLA compatible unrelated donors.
Active Comparator: Blood Stem Cell Transplant
Peripheral blood stem cell transplantation
Biological: Peripheral blood stem cell transplantation
Peripheral blood transplant from HLA compatible unrelated donors.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Two-year Overall Survival
Time Frame: Measured at 2 years
Overall survival rate at 2 years according to an intention-to-treat analysis.
Measured at 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Neutrophil Engraftment
Time Frame: Measured at Day 28
Measured at Day 28
Platelet Engraftment
Time Frame: Measured at Day 180
Measured at Day 180
Graft Failure
Time Frame: Measured at 28 and 100 days
Measured at 28 and 100 days
Extensive Chronic Graft-versus-host Disease (GVHD)
Time Frame: Measured at 730 days
Measured at 730 days
Chronic GVHD
Time Frame: Measured at 2 years
Measured at 2 years
Relapse
Time Frame: Measured at 2 years
Analysis restricted to patients who received the transplant.
Measured at 2 years
Infections
Time Frame: Measured at 1 and 2 years
Number of infection reports per patient.
Measured at 1 and 2 years
Grades III-V Unexpected Adverse Events
Time Frame: Measured by 2 years
Measured by 2 years
Acute GVHD Grade II-IV
Time Frame: 100 days, 180 days
100 days, 180 days
Acute GVHD Grade III-IV
Time Frame: 100 days, 180 days
100 days, 180 days
Current Immunosuppressive (IS) Free Survival
Time Frame: Measured at 2 years
This outcome measure takes into account subsequent immunosuppressive therapy that may occur following discontinuation of initial immunosuppressive therapy.
Measured at 2 years
Immune Reconstitution
Time Frame: Measured at 100 days, 6 months, and 1 and 2 years
Measured at 100 days, 6 months, and 1 and 2 years
Donor Recovery of Baseline Complete Blood Count (CBC) and White Blood Cell Count (WBC) Differential
Time Frame: Measured at 1, 6, and 12 months
Measured at 1, 6, and 12 months
Donor Recovery to Baseline Toxicity Scores
Time Frame: Measured at 1, 6, and 12 months
Measured at 1, 6, and 12 months
Donor Quality of Life
Time Frame: Measured at 1, 6, and 12 months
Measured at 1, 6, and 12 months
Patient Quality of Life
Time Frame: Measured at baseline, 6 months, and 1, 2, and 5 years
Measured at baseline, 6 months, and 1, 2, and 5 years

Collaborators and Investigators

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

Sponsor

Medical College of Wisconsin

Collaborators

National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
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

January 1, 2004

Primary Completion (Actual)

April 1, 2013

Study Completion (Actual)

April 1, 2014

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 (Estimate)

January 4, 2023

Last Update Submitted That Met QC Criteria

December 7, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BMTCTN0201
  • 5U24CA076518 (U.S. NIH Grant/Contract)
  • U01HL069294-05 (NIH)
  • BMT CTN 0201 (Other Identifier: Blood and Marrow Transplant Clinical Trials Network)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Results will be published in a manuscript

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
  • Informed Consent Form (ICF)

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.

Clinical Trials on Leukemia

Clinical Trials on Allogeneic bone marrow transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Sweden

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe