Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Chronic Myelogenous Leukemia
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor 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 transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects and best dose of fludarabine, total-body irradiation, and donor stem cell transplant followed by cyclosporine and mycophenolate mofetil and to see how well they work in treating patients with chronic myelogenous leukemia.
|Leukemia||Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy||Phase 1 Phase 2|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Fludarabine and Low-Dose TBI Dose Escalation to Determine the Optimal Regimen for Achieving High Rates Engraftment of Unrelated Donor Peripheral Blood Stem Cell in Patients With Chronic Myeloid Leukemia - A Multi-Center Trial|
- Increase number of patients with donor T-cell chimerism from > 40% to 90% on day 28 post-transplant
- Reduce graft rejection rate to < 10% day 84 post-transplant
- Maintain acute graft-vs-host disease (GVHD) incidence of 10%
- Maintain nonrelapse mortality incidence of < 15% on day 200 post-transplant
- Rate of complete cytogenetic remission
- Probability of actuarial disease-free survival
|Study Start Date:||April 2005|
|Study Completion Date:||November 2007|
- Determine whether increasing the intensity of a nonmyeloablative conditioning regimen comprising fludarabine and total body irradiation allows achievement of a donor T-cell chimerism level of > 40% on day 28 post-transplantation in 90% or more of patients with chronic myelogenous leukemia undergoing allogeneic peripheral blood stem cell transplantation and immunosuppression comprising cyclosporine and mycophenolate mofetil.
- Determine the feasibility of reducing the day 84 graft rejection rate/graft failure to < 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the incidence of grade 4 acute graft-versus-host disease at < 10% in patients treated with this regimen.
- Determine the feasibility of maintaining the day 200 nonrelapse mortality rate at < 15% in patients treated with this regimen.
- Determine the rate of complete cytogenetic remission in patients treated with this regimen.
- Determine the probability of actuarial disease-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of mycophenolate mofetil and fludarabine in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine and total-body irradiation (TBI).
- Nonmyeloablative conditioning regimen: Patients receive fludarabine IV on days -4 to -2 OR days -6 to -2. Patients undergo TBI on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSCT): After the completion of TBI, patients undergo allogeneic PBSCT on day 0.
- Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 100 followed by a taper to day 177 in the absence of graft-versus-host disease (GVHD). Beginning within 4-6 hours after the completion of PBSCT, patients receive oral mycophenolate mofetil 2-3 times daily on days 0-40 followed by a taper to day 96 in the absence of GVHD.
Cohorts of 5-25 patients receive cumulative doses of fludarabine and escalating doses of TBI until 2 of 5, 3 of 10-15, 4 of 20, or 5 of 25 patients experience a day 28 post-transplant T-cell chimerism level ≤ 40% and/or a day 84 post-transplant graft rejection rate of > 10%.
After completion of study transplantation, patients are followed 3 times weekly for 3 months, at 6, 12, and 18 months, annually for 5 years, and then periodically thereafter.
PROJECTED ACCRUAL: A total of 5-75 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00119340
|United States, Washington|
|Veterans Affairs Medical Center - Seattle|
|Seattle, Washington, United States, 98108|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Principal Investigator:||Brenda Sandmaier, MD||Fred Hutchinson Cancer Research Center|