Nonmyeloablative Bone Marrow Transplants in Hematologic Malignancies: Dose Finding Study for Post-Transplant Immunosuppression
- Determine a minimal (short-duration) post-transplant immunosuppression regimen
comprising cyclophosphamide and/or mycophenolate mofetil with or without tacrolimus
that results in ≤ 20% incidence of grade II or higher acute graft-versus-host disease
(GVHD) in patients with hematologic malignancies undergoing nonmyeloablative allogeneic
bone marrow or peripheral blood stem cell transplantation from an HLA-identical related
- Determine the post-transplant immunosuppression regimen that results in < 10% incidence
of nonengraftment, defined as < 5% donor chimerism in peripheral blood at day 60, in
- Determine the incidence and severity of acute GVHD in patients treated with these
- Determine the frequency of mixed chimerism in patients treated with these regimens.
- Nonmyeloablative allogeneic bone marrow transplantation (BMT) or peripheral blood stem
cell transplantation (PBSCT): Patients receive fludarabine IV on days -4 to -2 and
undergo total-body irradiation on day -1. Patients undergo allogeneic BMT on day 0 or
PBSCT on day 0 (and days 1 and 2, if needed). Patients receive filgrastim (G-CSF)
beginning on day 5 and continuing until at least day 15 or until blood counts recover.
- Sequentially increasing levels of post-transplant immunosuppression: Cohorts of
patients are enrolled into 1 of the following regimens:
- Regimen 1 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on
day 3 only.
- Regimen 2 (post-BMT immunosuppression): Patients receive mycophenolate mofetil
(MMF) once on day 3 and then twice daily on days 4-32.
- Regimen 3 (post-BMT immunosuppression): Patients receive cyclophosphamide IV on
days 3 and 4 and MMF twice daily on days 4-33.
- Regimen 4 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and
MMF as in regimen 3.
- Regimen 5 (post-PBSCT immunosuppression): Patients receive cyclophosphamide and
MMF as in regimen 3 and tacrolimus twice daily on days 4-33.
Cohorts of approximately 10-20 patients receive sequentially increasing levels of
post-transplant immunosuppression until a minimal (short-duration) post-transplant
immunosuppression regimen is identified. The minimal post-transplant immunosuppression
regimen is defined as the regimen in which ≤ 3 of 10 or ≤ 6 of 20 patients develop grade II
or higher acute graft-versus-host disease AND ≤ 2 of 10 or ≤ 4 of 20 patients fail to
engraft 60 days post-transplantation. Once the minimal post-transplant immunosuppression
regimen is identified, an additional 10 patients are treated with that regimen.
Patients are followed for 60 days after transplantation.
PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Supportive Care
Post-transplant immunosuppression regimen with ≤ 20% incidence of a grade II-IV graft-versus-host-disease (GVHD) and < 10% incidence of nonengraftment (< 5% donor chimerism) at day 60 following transplant
Carol A. Huff, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
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