A Phase II Study of Sirolimus, Tacrolimus and Thymoglobulin, as Graft-versus-Host Prophylaxis in Patients Undergoing Unrelated Donor Hematopoietic Cell Transplantation
- To determine the incidence and severity of acute- and chronic-graft-versus-host disease
(GVHD) after HLA-matched or -mismatched unrelated donor hematopoietic peripheral blood
transplantation in patients with hematologic malignancies scheduled to receive
immunosuppressive combination of sirolimus, tacrolimus, and anti-thymocyte globulin as
- To determine the safety of this combination in the first six months post-transplant.
- To determine the time-to-engraftment, non-relapse mortality rate, overall and
disease-free survival, incidence of disease relapse, and incidence of opportunistic
infections with this GVHD prophylaxis.
OUTLINE: Patients are stratified according to conditioning regimen (fludarabine phosphate
and melphalan vs fractionated total-body irradiation [FTBI] and etoposide vs FTBI and
cyclophosphamide) and degree of donor/recipient HLA mismatch (high-risk vs low-risk).
- Conditioning regimen: Patients receive 1 of 3 standard conditioning regimens beginning
on day -9 or -8 and continuing to day -1 or 0.
- Peripheral blood stem cell transplantation: Patients receive HLA-matched or mismatched
unrelated donor peripheral blood stem cells on day 0.
- Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously
beginning on day -3 and then orally when tolerated, oral sirolimus on days -3 and -2,
anti-thymocyte globulin IV over 4-8 hours on days -3 to 0, and methotrexate* IV on days
1, 3, and 6. Tacrolimus and sirolimus continue for 3-6 months (with taper).
NOTE: *Only patients with high-risk HLA mismatch receive treatment with methotrexate.
After completion of study therapy, patients are followed periodically for up to 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Incidence and severity of acute and chronic graft-versus-host disease
6 months after transplant
Ryotaro Nakamura, MD
Beckman Research Institute
United States: Food and Drug Administration
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|Banner Good Samaritan Medical Center||Phoenix, Arizona 85006|