A Pilot Phase II Study of Sirolimus, Tacrolimus, Thymoglobulin and Rituximab as Graft-versus-Host-Disease Prophylaxis in Patients Undergoing Haploidentical and HLA Partially Matched Donor Hematopoietic Cell Transplantation
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) in patients
with hematologic malignancies undergoing donor peripheral blood stem cell
transplantation who are receiving sirolimus, tacrolimus, anti-thymocyte globulin, and
rituximab as GVHD prophylaxis.
- Assess time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive
days) and platelet count (> 20 x 10^9/L for 3 consecutive days) in these patients.
- Determine the safety, as defined by serious adverse events and adverse events related
to this immunosuppressive regimen, in the first 6 months after treatment.
- Assess the incidence of chronic GVHD measured within 2 years after transplantation.
- Assess overall and disease-free survival at 2 years after transplantation.
- Examine the incidence of opportunistic infections including fungal infections,
pneumocystis carinii pneumonia, and viral infections (cytomegalovirus, varicella zoster
virus, herpes simplex virus, BK virus, Epstein-Barr virus, and post-transplant
- Assess the incidence of thrombotic microangiopathy within 100 days of transplantation.
- Perform immunocorrelative studies, including T-cell, B-cell, NK-cell, regulatory cell,
and allo-reactive T-cell measurement studies via flow cytometry, at 30, 60, 90, and 180
days after transplantation.
OUTLINE: Patients receive rituximab IV on days -7 and 3, tacrolimus IV continuously (may
switch to orally when the patient is able to eat) and oral sirolimus beginning on day -3,
and anti-thymocyte globulin IV over 6 hours on days -3 to -1. Tacrolimus and sirolimus are
tapered at the discretion of the treating physician.
All patients also receive a standard transplant-preparative regimen and undergo
transplantation on day 0.
Blood samples are collected before the preparative regimen and at 30, 60, 90, and 180 days
after transplantation for correlative immunologic studies.
After completion of study treatment, patients are followed up for 2 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Incidence and severity of acute graft-vs-host disease (GVHD)
During the first six months post transplant
Zaid Al-Kadhimi, M.D.
Barbara Ann Karmanos Cancer Institute
United States: Institutional Review Board
|Karmanos Cancer Institute||Detroit, Michigan 48201|