Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors
- To assess the percentage of patients with hematological malignancies or renal cell
carcinoma who achieve > 90% donor T-cell chimerism at 30 days after treatment with
reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose
cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral
blood progenitor cell transplantation from a matched related donor.
- To assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
and extensive chronic GVHD in these patients.
- To assess whether this regimen is associated with reduced transplant-related toxicity
and increased tolerability in these patients.
- To assess the overall safety of this conditioning regimen as measured by 6-month
transplant-related mortality in these patients.
- To determine the efficacy of this regimen in inducing durable remissions in these
- Reduced-intensity conditioning (RIC): Patients receive anti-thymocyte globulin IV over
4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate IV over 30
minutes on days -7 to -3, busulfan IV over 3 hours on days -4 and -3, and
cyclophosphamide IV over 1-2 hours on day -2.
- Transplantation: Patients undergo allogeneic peripheral blood progenitor cell
transplantation on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus every 12
hours on days -1 to 90, followed by a taper until day 150. Patients also receive
methotrexate IV on days 1, 3, and 6.
Blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte
globulin and PCR analysis for chimerism.
After completion of study therapy, patients are followed periodically for up to 3 years.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Asad Bashey, MD, PhD
Blood and Marrow Transplant Group of Georgia
United States: Food and Drug Administration
|Blood and Marrow Transplant Group of Georgia||Atlanta, Georgia 30342-1601|