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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
551
Bone marrow transplant from HLA compatible unrelated donors.
Peripheral blood transplant from HLA compatible unrelated donors.
University of Alabama at Birmingham
Birmingham, Alabama, United States
City of Hope National Medical Center
Duarte, California, United States
UCSD Cancer Center
La Jolla, California, United States
University of California, San Francisco
San Francisco, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
Two-year Overall Survival
Overall survival rate at 2 years according to an intention-to-treat analysis.
Time frame: Measured at 2 years
Neutrophil Engraftment
Time frame: Measured at Day 28
Platelet Engraftment
Time frame: Measured at Day 180
Graft Failure
Time frame: Measured at 28 and 100 days
Extensive Chronic Graft-versus-host Disease (GVHD)
Time frame: Measured at 730 days
Chronic GVHD
Time frame: Measured at 2 years
Relapse
Analysis restricted to patients who received the transplant.
Time frame: Measured at 2 years
Infections
Number of infection reports per patient.
Time frame: Measured at 1 and 2 years
Grades III-V Unexpected Adverse Events
Time frame: Measured by 2 years
Acute GVHD Grade II-IV
Time frame: 100 days, 180 days
Acute GVHD Grade III-IV
Time frame: 100 days, 180 days
Current Immunosuppressive (IS) Free Survival
This outcome measure takes into account subsequent immunosuppressive therapy that may occur following discontinuation of initial immunosuppressive therapy.
Time frame: Measured at 2 years
Immune Reconstitution
Time frame: 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
Donor Recovery to Baseline Toxicity Scores
Time frame: Measured at 1, 6, and 12 months
Donor Quality of Life
Time frame: Measured at 1, 6, and 12 months
Patient Quality of Life
Time frame: Measured at baseline, 6 months, and 1, 2, and 5 years
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University of Florida College of Medicine (Shands)
Gainesville, Florida, United States
Emory University
Atlanta, Georgia, United States
Loyola University
Maywood, Illinois, United States
IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health
Indianapolis, Indiana, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
...and 35 more locations