Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy
- Determine if a nonmyeloablative regimen comprising cyclophosphamide, fludarabine, and
radiotherapy followed by cyclosporine and mycophenolate mofetil provides a prompt and
durable donor engraftment in patients with hematologic malignancies or kidney cancer
who are undergoing allogeneic stem cell transplantation.
- Determine the safety of this nonmyeloablative transplantation regimen in these
- Determine the risk of graft-versus-host-disease in patients treated with this regimen.
- Determine the antineoplastic potency of nonmyeloablative stem cell transplantation in
patients treated with this regimen.
- Determine the effect of lower doses of daily fludarabine on treatment-related mortality
(TRM) OUTLINE: Patients are stratified according to risk (standard vs high).
- Preparative regimen*: Patients receive cyclophosphamide intravenously (IV) over 2 hours
on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients undergo total body
irradiation on day -1. Some patients also receive anti-thymocyte globulin (ATG)** IV
every 12 hours on days -6 to -4. Patients who receive ATG* include the following:
- Related donor recipients who have not received combination chemotherapy within the
past 6 months
- Unrelated donor recipients who have not received combination chemotherapy within
the past 3 months
- Unrelated donor recipients who have received only 1 induction course for the
treatment of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML),
myelodysplastic syndromes (MDS), or blastic phase chronic myelogenous leukemia
(CML) NOTE: **Patients who underwent prior autologous stem cell transplantation in
the past year do not receive ATG.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo
allogeneic PBSCT on day 0.
- Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV over 2 hours
beginning on day -3 and continuing until at least day 100. Patients also receive
mycophenolate mofetil IV or orally twice daily on days -3 to 30.
- Donor lymphocyte infusion (DLI): Patients without active GVHD but deteriorating donor
chimerism may receive DLI IV over 2 hours.
After completion of study treatment, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Neutrophil and Donor Cell Engraftment
Successful sustained engraftment is defined as primary neutrophil engraftment by day 42 and e90% donor cells at day 100, with or without DLI. Engraftment based on absolute neutrophil count of donor origin > 0.5 x 10e9 /L for 3 days by day 42
Day 42 and Day 100
Erica Warlick, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|