Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide
- Determine the minimum effective dose of pretransplant cyclophosphamide to induce
engraftment of haploidentical allogeneic bone marrow without the use of myeloablative
conditioning in patients with hematologic malignancies.
- Determine the incidence and severity of graft versus host disease and nonhematologic
toxicities with this treatment regimen in these patients.
- Correlate the pretreatment phenotypic and functional immunologic characteristics in
these patients in relation to risk of graft rejection with this treatment regimen.
OUTLINE: This is a dose-escalation study of cyclophosphamide.
Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1
hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow
transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days
4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV
starting on day 4 and continuing until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum
effective dose necessary to induce chimerism without unacceptable toxicity in these patients
Patients are followed at 2 and 6 months, at one year, and then annually thereafter.
PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.
Primary Purpose: Treatment
Ephraim J. Fuchs, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|