A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched Bone Marrow for Patients With Hematologic Malignancies
- Determine transplant-related mortality, risk of relapse, and progression-free survival
of patients with standard- or high-risk hematologic malignancies undergoing
nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body
irradiation followed by HLA-haploidentical allogeneic bone marrow transplantation.
- Determine donor hematopoietic chimerism in patients' peripheral blood at 30, 60, and
180 days after transplantation.
- Determine hematologic and nonhematologic toxic effects of this regimen in these
- Determine, when feasible, surface expression of HLA molecules and death receptors,
sensitivity to cytotoxic lymphocytes, and expression of anti-apoptotic genes (e.g.,
Bcl-2, Bcl-xL, X-IAP, and c-FLIP) in cancer cells from patients who relapse after
treatment with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse
(standard [defined as ≤ 30% risk] vs high [defined as ≥ 70% risk]).
- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes
on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients
undergo total body irradiation on day -1.
- Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on
- Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on
days 3 and 4.
- Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral
mycophenolate mofetil 3 times daily until day 35 and tacrolimus IV (then changing to
orally) twice daily until day 180.
Treatment continues in the absence of disease progression.
After completion of study transplantation, patients are followed on days 30, 60, 100, and
180; at 1 year; and then annually for 4 additional years.
PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4
Masking: Open Label, Primary Purpose: Treatment
Transplant-related mortality at 60 days, 6 months, 1 and 2 years
Ephraim J. Fuchs, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Hahnemann University Hospital||Philadelphia, Pennsylvania 19102-1192|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|
|Blood and Marrow Transplant Program at Northside Hospital||Atlanta, Georgia 30342|