A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin®, as Graft-versus-Host- Disease Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
- To determine the incidence and severity of acute graft-versus-host disease (GVHD) after
HLA-matched or -mismatched unrelated donor peripheral blood stem cell transplantation
(PBSCT) in patients with hematologic malignancies treated with immunosuppressive
therapy comprising sirolimus, tacrolimus, and anti-thymocyte globulin as GVHD
- To determine the safety of this regimen in these patients at 6 months after PBSCT.
- To determine the time to engraftment (i.e., platelet and absolute neutrophil recovery)
in patients treated with this regimen.
- To determine the length of hospital stay of these patients within 100 days after PBSCT.
- To determine the incidence of infections, including CMV and EBV reactivation and
post-transplant lymphoproliferative disorders, in patients treated with this regimen.
- To determine the incidence of thrombotic microangiopathy and veno-occlusive disease in
patients treated with this regimen.
- To determine the incidence of chronic GVHD in patients treated with this regimen.
- To determine the overall and disease-free survival of these patients at 2 years after
- To determine the Karnofsky performance status of these patients at baseline and at
various time points after PBSCT.
- To conduct immunocorrelative studies prior to and at various time points after PBSCT.
- Conditioning regimen: Patients receive 1 of 6 conditioning regimens between days -9 and
-3, based on diagnosis and the treating physician's preference regarding regimen
- Regimen I: Patients receive fludarabine phosphate IV and busulfan IV.
- Regimen II: Patients undergo total body irradiation (TBI) twice daily for 8
fractions and receive etoposide IV.
- Regimen III: Patients undergo TBI once or twice daily for 11 fractions and receive
- Regimen IV: Patients undergo TBI and receive fludarabine phosphate IV and busulfan
- Regimen V: Patients receive carmustine IV, etoposide IV, cytarabine IV, and
melphalan IV. Some patients also receive rituximab IV.
- Regimen VI: Patients receive fludarabine phosphate IV and melphalan IV. Some
patients also undergo TBI.
- Allogeneic peripheral blood stem cell transplantation: Patients undergo filgrastim
(G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.
- Graft-versus-host disease prophylaxis (GVHD): Patients receive tacrolimus IV
continuously over 24 hours or orally and sirolimus orally beginning on day -3 and
continuing until day 30 or day 90, followed by a taper in the absence of GVHD. Patients
also receive anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
Blood samples are obtained at baseline and periodically during study for correlative
biomarker studies. Samples are analyzed by T-cell immunophenotyping, absolute subset number
quantification, and multi-parameter flow cytometry for evaluation of immune reconstitution,
T-cell differentiation status, NK-cell recovery, allo-reactivity of donor T-cells after
transplantation, and regulatory T-cell reconstitution.
After completion of study therapy, patients are followed periodically for up to 2 years.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Incidence and severity of acute graft-versus-host disease (GVHD)
Within 100 days after donor peripheral blood stem cell transplantation (PBSCT) as assessed by Glucksberg criteria
Zaid Al-Kadhimi, MD
Barbara Ann Karmanos Cancer Institute
United States: Federal Government
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|