Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Non-Myeloablative Preparative Regimen
- Determine the one- and two-year survival of patients with hematologic malignancies
treated with a nonmyeloablative conditioning regimen comprising fludarabine,
cyclophosphamide, and total-body irradiation followed by umbilical cord blood
transplantation and post-transplant immunosuppression comprising sirolimus and
- Determine the six-month nonrelapse mortality of patients treated with this regimen.
- Determine the presence of chimerism in patients treated with this regimen at days 21,
60, 100, 180, and 365.
- Determine the incidence of neutrophil engraftment by day 42 in patients treated with
- Determine the incidence of platelet engraftment by six months in patients treated with
- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease
(GVHD) at day 100 in patients treated with this regimen.
- Determine the incidence of chronic GVHD at one year in patients treated with this
- Determine the probability of overall survival within one or two years in patients
treated with this regimen.
- Determine the probability of progression-free survival within one or two years in
patients treated with this regimen.
- Determine the incidence of relapse or disease progression within one or two years in
patients treated with this regimen.
OUTLINE: This is a nonrandomized study. Patients are stratified according to disease (acute
myeloid leukemia, myelodysplastic syndromes, chronic myelogenous leukemia [CML] in first
chronic phase and second chronic phase [CP2] after myeloid blast crisis vs acute
lymphoblastic leukemia, CML CP2 post lymphoid blast crisis, lymphoblastic lymphoma, and
Burkitt's lymphoma vs large cell B- and T-cell lymphomas and mantle cell lymphoma vs chronic
lymphocytic leukemia, marginal zone B-cell lymphoma, follicular lymphoma, small lymphocytic
lymphoma, lymphoplasmacytic lymphoma, and prolymphocytic leukemia vs Hodgkin's lymphoma and
- Nonmyeloablative conditioning: Patients receive fludarabine intravenously (IV) over 1
hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients who did
not undergo prior autologous transplant or who received ≤ 1 course of prior multiagent
chemotherapy or no severely immunosuppressive therapy in the past 3 months also receive
anti-thymocyte globulin IV over 4-6 hours twice daily on days -6 to -4. All patients
also undergo total-body irradiation on day -1.
- Umbilical cord blood transplant: Patients undergo umbilical cord blood transplantation
on day 0.
- Post-transplant immunosuppression: Sirolimus will be administered starting at day -3
with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum
concentration of 3 to 12 mg/mL. Levels are to be monitored 3 times/week in the first 2
weeks, weekly until day +60, and as clinically indicated until day +100
post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at
day +100 and eliminated by day +180 post-transplantation. Patients also receive
mycophenolate mofetil IV on days -3 to 5 and then orally on days 6-30.
After completion of study treatment, patients are followed periodically for 5 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
Number of patients alive at 1 and 2 years post transplant
1 Year, 2 Years
Claudio G. Brunstein, MD, PhD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|