A Phase II Study of Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors for Treatment of Hematologic Malignancies and Hematopoietic Failure States
Fewer than 35% of patients who might benefit from allogeneic HCT have an HLA-identical sib.
Transplantation of peripheral blood stem cells (PBSCs) or bone marrow (BM)from HLA-matched
or one-locus mismatch unrelated volunteer donors may be an alternative in some patients who
lack HLA-matched sib donors. Despite increasing numbers of volunteer unrelated donors in
national and international registries, identification of suitable unrelated donors who are
matched with the recipient at all HLA-A, -B, -C and -DRB1 loci (8/8 HLA match) or mismatched
at one of those loci (7/8 HLA match) is still challenging, especially for patients who are
African-American or multiracial. Additionally, the 3- to 4-month delay between initiation
of unrelated donor search to HCT is unacceptably long in patients with aggressive
hematologic malignancies that are likely to relapse or progress during that interval.
Transplantation of single or dual unrelated umbilical cord blood cells (UCB) units is
another alternative, although problems with inadequate cell doses, delayed engraftment,
graft rejection and infection persist in adult recipients of unrelated UCB transplants.
This is a phase II single-arm open-label study to evaluate the efficacy and safety of
haploidentical related allogeneic PBSCT using a nonmyeloablative preparative regimen of
intravenous busulfan (Busulfex®), intravenous melphalan (Alkeran®) and intravenous
alemtuzumab (Campath®) in subjects who are candidates for related or unrelated allogeneic
hematopoietic cell transplantation (HCT; transplantation of bone marrow or PBSCs) but who
lack histocompatible related or unrelated donors. This study will also evaluate
immunological reconstitution following haploidentical PBSCT by measurement of circulating T
cell receptor excision circle (TREC)-positive cells, an indicator of thymic output.
Systematic analyses of TREC-positive cells have not been performed in recipients of
haploidentical PBSCT after the preparative regimen described in this protocol.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood)in peripheral blood by day +100.
by day +100 (i.e., 100 days after haploidentical PBSCT).
Andrew M Yeager, MD
University of Arizona
United States: Institutional Review Board
|Arizona Cancer Center/University Medical Center||Tucson, Arizona 85719|