Allogeneic Mixed Chimerism Stem Cell Transplantation Utilizing In Vivo and In Vitro Campath for Hemoglobinopathies and Bone Marrow Failure Syndromes
1. Evaluate the feasibility in terms of mortality, occurrence of acute graft versus host
disease, and grades 3-4/4 toxicity of in vivo and in vitro Campath coupled with
concomitantly administered nonmyeloablative fludarabine, cyclophosphamide and total
body irradiation (TBI) followed by Human Leukocyte Antigen (HLA) 5-6/6 matched family
member allo peripheral blood stem cell transplant (PBSCT).
2. Evaluate the engraftment rate of HLA 5-6/6 matched family member patients who receive
in vivo Campath followed by concomitantly administered fludarabine, cyclophosphamide
and total body irradiation (TBI) as a conditioning regimen with Campath-treated
peripheral blood stem cells (in vitro and in vivo exposure).
1. Evaluate the response rate and survival of patients who receive a non-myeloablative
conditioning regimen of in vivo Campath followed by concomitantly administered
fludarabine, cyclophosphamide and total body irradiation (TBI) with Campath-treated
peripheral blood stem cells.
2. Evaluate the recovery of immune function post engraftment with this regimen.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Engraftment rate as indicated by chimerism studies
Absolute Neutrophil Count (ANC) > 500/μL and platelets > 20,000/μL and hemoglobin level remaining above 10 g/dL without transfusion support, with tests showing at least 2.5% donor cells present. Primary graft failure is defined as absence of establishment of adequate donor hematopoiesis by day 42 with bone marrow cellularity < 5%, peripheral White Blood Count (WBC) < 500/μL, peripheral ANC < 100/μL, and/or platelets < 10,000/μL by day 120 with absence of megakaryocytes in the bone marrow (in the absence of disease relapse). Mixed chimerism is defined as 2.5% to 97.5% donor stem cells in the microchimerism, Restriction Fragment Length Polymorphism (RFLP), or Florescence In Situ Hybridization (FISH) assay used to determine the origination of the stem cells (donor or recipient).
1 year post transplant
David A. Rizzieri, MD
Duke Cancer Institute
United States: Federal Government
|Florida Hospital Cancer Institute||Orlando, Florida 32804|
|Duke Cancer Institute||Durham, North Carolina 27710|