Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer
RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.
|Chronic Myeloproliferative Disorders Leukemia Lymphoma Myelodysplastic Syndromes||Biological: filgrastim Biological: graft-versus-tumor induction therapy Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: umbilical cord blood transplantation Radiation: radiation therapy|
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Cyclophosphamide/Fludarabine/Total Body Irradiation Preparative Regimen for Patients With Hematological Malignancy Receiving Unrelated Donor Umbilical Cord Blood Transplantation|
- Engraftment as measured by an absolute neutrophil count of donor origin > 0.5 x 109 /L for 3 days by day 42
- Incidence and severity of acute or chronic graft-versus-host-disease, relapse, or mortality at day 100
- Survival and event-free survival by Kaplan-Meier estimation at 1 and 2 years after umbilical cord blood (UCB) transplant
|Study Start Date:||April 2001|
|Study Completion Date:||January 2006|
|Primary Completion Date:||January 2006 (Final data collection date for primary outcome measure)|
- Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.
- Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
- Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
- Determine the incidence of malignant relapse in patients treated with this regimen.
- Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
- Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).
- Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
- Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
- Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00290641
|United States, Minnesota|
|University of Minnesota Cancer Center|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Claudio G. Brunstein, MD, PhD||Masonic Cancer Center, University of Minnesota|