Phase I Study of T Cell Depleted (TCD) Partially Matched Related Donor (PMRD) Hematopoietic Stem Cell Transplantation for High Risk Hematologic Diseases Using Intense Pre and Post Transplant Immunosuppression and Megadose CD34 "Veto" Cells
OBJECTIVES: I. Determine if megadose CD34 cells and intense immunosuppression administered
before and after partially matched related donor (PMRD) hematopoietic stem cell (HSC)
transplantation results in engraftment in patients with high risk hematologic malignancies.
II. Determine the incidence and severity of acute grade (I-IV) and chronic (limited or
extensive) graft versus host disease in patients after rigorous T-cell depletion in PMRD HSC
OUTLINE: Harvest: Bone marrow and peripheral blood stem cells (PBSC) are harvested from a
related 1, 2, or 3 HLA antigen mismatched donor. PBSC are selected for CD34+ cells and
T-cells are depleted. Conditioning: Patients undergo total body irradiation twice daily on
days -10 to -7 and once on day -6. Patients receive cladribine IV continuously on days -10
to -6; etoposide IV over 2 hours on day -5; and cyclophosphamide IV over 2 hours,
antithymocyte globulin (ATG) IV over 10-12 hours, and methylprednisolone IV over 1 hour on
days -4 to -2. Transplantation: T-cell depleted PBSC and bone marrow are infused on day 0.
Patients receive G-CSF SQ daily beginning on day 0 and continuing until blood counts
recover. Graft versus host disease prophylaxis: Patients receive tacrolimus IV every 12
hours beginning on day -2 and continuing orally 4 times a day for 6-12 months at the
discretion of the protocol investigator. Patients receive ATG IV over 10-12 hours and
methylprednisolone IV over 1 hour on days 5-15 followed by a taper of methylprednisolone.
Patients are followed every week through day 100 and then at 6 and 12 months.
PROJECTED ACCRUAL: A total of 12-20 patients will be accrued for this study within 3 years.
Primary Purpose: Treatment
Richard K. Burt, MD
Robert H. Lurie Cancer Center
United States: Federal Government
|Robert H. Lurie Comprehensive Cancer Center, Northwestern University||Chicago, Illinois 60611|