HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies
- Determine the optimal dose of post-transplant immunosuppression comprising high-dose
cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after
myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide
followed by allogeneic bone marrow transplantation in patients with high-risk
- Determine the incidence and severity of acute graft-versus-host disease in patients
treated with this regimen.
- Determine other toxic effects of this regimen in these patients.
- Determine immune reconstitution in patients treated with this regimen.
- Determine disease control in patients treated with this regimen.
OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs
> 19 years old).
- Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times
daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily
on days -3 to -1 OR days -2 and -1.
- Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow
transplantation on day 0.
- Immunosuppression therapy: Patients receive 1 of the following immunosuppressive
- Regimen 1: Patients receive high-dose cyclophosphamide IV over 1 hour on day 3.
- Regimen 2: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3
- Regimen 3: Patients receive high-dose cyclophosphamide as in regimen 2 and oral
mycophenolate mofetil three times daily on days 5-35.
- Regimen 4: Patients receive high-dose cyclophosphamide as in regimen 2 and
mycophenolate mofetil as in regimen 3. Patients also receive tacrolimus IV or
orally twice daily on days 5-50.
After completion of study transplantation, patients are followed at 30 and 60 days, 6
months, 1 year, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 30-60 patients (approximately 5 per immunosuppressive
treatment regimen) will be accrued for this study.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To find the optimal dose of post-grafting immunosuppression with high-dose cyclophosphamide (Cy), FK-506 and MMF following myeloablative fully HLA-matched related or unrelated BMT for the patients with hematological malignancies who are at high risk of relapse. To estimate the incidence and severity of acute GVHD and other toxicities following myeloablative fully HLA-matched related or unrelated BMT using this approach for the patients with hematological malignancies
Leo Luznik, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Food and Drug Administration
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|