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

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.

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