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

Phase 3

Completed

Conditions: Myelodysplastic-Myeloproliferative Diseases
Leukemia
Myeloproliferative Disorders

Interventions: Biological: Allogeneic bone marrow transplantation
Biological: Peripheral blood stem cell transplantation

Registration Number: NCT00075816

Lead Sponsor: Medical College of Wisconsin

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 551

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bone Marrow Transplant	Allogeneic bone marrow transplantation	Allogeneic bone marrow transplantation
Blood Stem Cell Transplant	Peripheral blood stem cell transplantation	Peripheral blood stem cell transplantation

Primary Outcome Measures

Name	Time	Method
Two-year Overall Survival	Measured at 2 years	Overall survival rate at 2 years according to an intention-to-treat analysis.

Secondary Outcome Measures

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

Trial Locations

Locations (45): Emory University
🇺🇸
Atlanta, Georgia, United States
Loyola University
🇺🇸
Maywood, Illinois, United States
Hackensack University Medical Center Cancer Center
🇺🇸
Hackensack, New Jersey, United States
University of Toronto, Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
University of California, San Francisco
🇺🇸
San Francisco, California, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Pittsburgh Cancer Institute
🇺🇸
Pittsburgh, Pennsylvania, United States
Vanderbilt University
🇺🇸
Nashville, Tennessee, United States
Baylor College of Medicine/The Methodist Hospital
🇺🇸
Houston, Texas, United States
University of Texas/MD Anderson CRC
🇺🇸
Houston, Texas, United States
Texas Transplant Institute
🇺🇸
San Antonio, Texas, United States
Utah BMT/Primary Children's Medical Center
🇺🇸
Salt Lake City, Utah, United States
Utah BMT/University of Utah Medical School
🇺🇸
Salt Lake City, Utah, United States
University of Kansas Hospital
🇺🇸
Kansas City, Kansas, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Oklahoma Medical Center
🇺🇸
Oklahoma City, Oklahoma, United States
Mayo Clinic Cancer Center
🇺🇸
Rochester, Minnesota, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
University of Michigan Medical Center
🇺🇸
Ann Arbor, Michigan, United States
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
UCSD Cancer Center
🇺🇸
La Jolla, California, United States
Stanford Hospital and Clinics
🇺🇸
Stanford, California, United States
University of Florida College of Medicine (Shands)
🇺🇸
Gainesville, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health
🇺🇸
Indianapolis, Indiana, United States
DFCI/Brigham & Women's
🇺🇸
Boston, Massachusetts, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Washington University/Barnes Jewish Hospital
🇺🇸
Saint Louis, Missouri, United States
Washington University/St. Louis Children's Hospital
🇺🇸
Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Cohen Children's Hospital
🇺🇸
New Hyde Park, New York, United States
Ohio State/Arthur G. James Cancer Hospital
🇺🇸
Columbus, Ohio, United States
Oregon Health & Science University (Peds)
🇺🇸
Portland, Oregon, United States
Oregon Health Sciences University
🇺🇸
Portland, Oregon, United States
University of Pennsylvania Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Tom Baker Cancer Centre, Calgary
🇨🇦
Calgary, Alberta, Canada
Virginia Commonwealth University MCV Hospitals
🇺🇸
Richmond, Virginia, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Ottawa Hospital
🇨🇦
Ottawa, Ontario, Canada
Vancouver General Hospital
🇨🇦
Vancouver, British Columbia, Canada
Hamilton Health Sciences - McMaster Site
🇨🇦
Hamilton, Ontario, Canada
Queen Elizabeth II Health Sciences Centre - Halifax
🇨🇦
Halifax, Canada
Baylor University Medical Center
🇺🇸
Dallas, Texas, United States