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
I. Incidence and severity of acute GVHD (aGVHD). II. To determine time to engraftment
absolute neutrophil count (ANC) (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20
X 10^9/L for 3 consecutive days).
III. Safety defined by serious adverse events (SAE) and adverse events (AE) related to this
immunosuppressive regimen in the first six months post transplant.
I. Incidence of chronic GVHD (cVHD) measured within two years after transplant. II. Overall
and disease-free survival at two years post hematopoietic cell transplantation (HCT).
III. Incidence of opportunistic infections, defined as infection that occurs in people with
weakened immune systems and caused by an organism that does not normally cause disease.
These include: fungal infections, pneumocystis carinii pneumonia (PCP), and viral infections
(cytomegalovirus [CMV], varicella zoster virus [VZV], herpes simplex virus [HSV], BK virus
[BK], Epstein-Barr virus [EBV] including post-transplant lymphoproliferative disorder
IV. Incidence of thrombotic microangiopathy within 100 days of HCT. V. Immunocorrelative
studies: T-cell, B cell, natural-killer (NK) cell, regulatory cell, and allo-reactive T cell
quantitation studies, using flow cytometry at 30, 60, 90, and 180 days post transplant.
Patients receive rituximab intravenously (IV) over 90 minutes on day -7 and 3, tacrolimus IV
continuously or orally (PO) once daily (QD), sirolimus PO QD beginning on day -3 with taper,
and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
After completion of study treatment, patients are followed up on days 30, 60, 90, 180 and
then 1 and 2 years thereafter.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Incidence and severity of aGVHD rate
aGVHD will be estimated using cumulative incidence function; the Glucksberg scale will be used to grade aGVHD.
For 6 months
Barbara Ann Karmanos Cancer Institute
United States: Food and Drug Administration
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|