Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells
- Determine the feasibility and efficacy of a reduced-intensity conditioning regimen
comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic
peripheral blood stem cell transplantation (PBSCT) in patients with hematologic
- Determine the toxicity of this regimen in these patients.
- Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells,
administered after allogeneic PBSCT, in these patients.
OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted
donor T cells.
- T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood
mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are
irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order
to selectively deplete T cells from the donor PBMCs.
- Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5,
fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day
-4, and thiotepa IV on days -3 to -2.
- Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1.
- Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo
allogeneic PBSC transplantation on day 0.
- LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2
immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on
approximately day 28.
Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated,
selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The
MTD is defined as the dose preceding that at which 2 of 6 patients experience
After completion of study treatment, patients are followed weekly for 100 days
post-transplantation and then periodically for survival.
PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.
Primary Purpose: Treatment
Erkut Bahceci, MD
United States: Federal Government
|Yale Cancer Center||New Haven, Connecticut 06520-8028|