Primary Outcome Measures:
- Neutrophil recovery at day +28
100 day survival (Stage I) [ Designated as safety issue: No ]
- Incidence of grade II-IV acute GVHD at day 100 (Stage II) [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Incidence of grade III-IV acute GVHD at day 100 [ Designated as safety issue: No ]
- Incidence of chronic GVHD at 6 months [ Designated as safety issue: No ]
- Relapse at 6 months [ Designated as safety issue: No ]
- Survival at 100 days and 1 year [ Designated as safety issue: No ]
- Comparison of other endpoints after transplant using KIR-ligand
mismatched vs. matched donors [ Designated as safety issue: No ]
- Incidence of toxicity associated with the use of bortezomib [ Designated as safety issue: Yes ]
OBJECTIVES:
Primary
- To determine whether administration of donor NK Cells can permit engraftment and satisfactory 100 day survival after haploidentical hematopoietic stem cell transplantation (HSCT).
Secondary
- To determine the incidence of multiorgan toxicity, engraftment, acute and chronic GVHD, relapse, transplant-related (non-relapse) mortality and survival after transplantation.
- To compare these endpoints after transplantation using KIR-L matched vs. mismatched donors and in recipients missing 0, 1 or 2 KIR-L.
- To evaluate the safety of adding bortezomib (Velcade) to the preparative regimen.
OUTLINE: This is an open-label study.
Patients receive fludarabine IV over 1 hour daily on days -17 to -13, cyclophosphamide IV over 2 hours on day -13, and undergo total body irradiation on day -12. Patients then receive an infusion of donor natural killer cells on day -12 and receive interleukin-2 on alternating days on days -10 to -2 and undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients also receive anti-thymocyte globulin IV over 4-6 hours on days 0-2.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Purpose
