Combination Chemotherapy and Total-Body Irradiation Before Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer, Metastatic Breast Cancer, or Kidney Cancer
RATIONALE: Giving low doses of chemotherapy 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 when they do not exactly match the patient's blood. 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 antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving combination chemotherapy together with total-body irradiation before donor umbilical cord blood transplant and to see how well they work in treating patients with advanced hematologic cancer, metastatic breast cancer, or kidney cancer.
|Breast Cancer Kidney Cancer Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes||Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: radiation therapy Procedure: umbilical cord blood transplantation||Phase 1 Phase 2|
|Study Design:||Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Hematological Diseases Using a Non-Myeloablative Preparative Regimen|
- Safety as assessed by a non-relapse mortality < 30% within day 100
- Hematopoietic recovery and the degree of chimerism at days 21, 60, 100, 180, and 360 after study completion
|Study Start Date:||June 2000|
|Study Completion Date:||December 2005|
|Primary Completion Date:||December 2005 (Final data collection date for primary outcome measure)|
- Determine the safety of nonmyeloablative preparative regimen comprising cyclophosphamide, fludarabine, and total-body irradiation with or without anti-thymocyte globulin, in terms of non-relapse mortality at day 100 post-transplantation, in patients with advanced hematologic malignancies, metastatic breast cancer, or renal cell cancer who are undergoing umbilical cord blood transplantation from an unrelated donor.
- Determine the hematopoietic recovery and degree of chimerism on days 21, 60, 100, 180, and 360 post-transplantation.
- Determine the incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) by day 100 post-transplantation and chronic GVHD at 1 year post-transplantation.
- Evaluate the risk of relapse at 1 year post-transplantation.
- Determine overall survival at 1 year post-transplantation.
- Nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine IV over 1 hour on days -6 to -2. Patients also undergo total-body irradiation on day -1. Some patients* may also receive anti-thymocyte globulin (ATG) IV twice daily on days -6 to -4.
NOTE: *Patients who have not had prior combination chemotherapy within the past 3 months OR who only received 1 prior induction course for the treatment of acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndromes, or chronic myelogenous leukemia in blast crisis receive ATG during the preparative regimen.
- Umbilical cord blood transplantation (UCBT): Patients undergo UCBT from an unrelated donor on day 0.
- Graft-versus-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day -3 and continuing until day 30 or until 7 days after engraftment.
After transplantation, patients are followed periodically for 2 years.
PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00365287
|Study Chair:||Claudio G. Brunstein, MD, PhD||Masonic Cancer Center, University of Minnesota|