Donor Umbilical Cord Blood Transplant After Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease
Recruitment status was: Recruiting
RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of abnormal 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 cells and help destroy any remaining abnormal 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 before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of donor umbilical cord blood transplant after cyclophosphamide, fludarabine phosphate, and total-body irradiation in treating patients with hematologic disease.
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Other: laboratory biomarker analysis
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: umbilical cord blood transplantation
Radiation: total-body irradiation
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen|
- Non-relapse mortality at day 100 [ Designated as safety issue: No ]
- Incidence of grades II-IV and III-IV acute graft-vs-host disease (GVHD) at day 100 and chronic GVHD at 1 year [ Designated as safety issue: No ]
- Mixed chimerism [ Designated as safety issue: No ]
- Hemopoietic recovery [ Designated as safety issue: No ]
|Study Start Date:||January 2009|
|Estimated Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
- To assess the safety and efficacy of unrelated-donor umbilical cord blood transplantation (UCBT) using a nonmyeloablative preparative regimen in patients with hematological disease, in a multi-institution UK setting.
- To confirm that unrelated-donor UCBT following nonmyeloablative conditioning is associated with consistent and durable engraftment in these patients.
- To assess transplant-related mortality at day 100 associated with nonmyeloablative UCBT in these patients.
- To assess the incidence of grades II-IV and III-IV acute graft-vs-host disease (GVHD) in these patients.
- To assess the risk of relapse and progressive disease in these patients at 1 year post transplant after nonmyeloablative UCBT.
- To assess overall and progression-free survival of these patients at 1 year after nonmyeloablative UCBT.
- To assess immune reconstitution at 1, 2, 3, 6, 12, and 24 months after transplant as measured by quantitative recovery of B, T, and NK cells (flow cytometry), qualitative recovery of T cells (TREC and spectratyping), in vivo functional T-cell responses (EBV and CMV tetramers), and quantitative immunoglobulins.
OUTLINE: This is a multicenter study.
- Reduced-intensity conditioning regimen: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -2. Patients undergo a single fraction of total-body irradiation on day -1.
- Umbilical cord blood (UCB) transplantation: Patients undergo umbilical cord blood transplantation on day 0.
- Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV or orally on days -3 to 100 followed by taper and mycophenolate mofetil IV or orally on days -3 to 35 followed by taper.
Blood and bone marrow samples are collected periodically for analysis.
After completion of study treatment, patients are followed up every 3 months in year 1, every 4 months in year 2, every 6 months until 5 years, and then annually thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00959231
|Bristol Royal Hospital for Children|
|Bristol, England, United Kingdom, BS2 8BJ|
|Cancer Research UK Clinical Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS16 6QB|
|University College of London Hospitals|
|London, England, United Kingdom, NW1 2PQ|
|UCL Cancer Institute|
|London, England, United Kingdom, WC1E 6DD|
|Great Ormond Street Hospital for Children|
|London, England, United Kingdom, WC1N 3JH|
|University of Newcastle-Upon-Tyne Northern Institute for Cancer Research|
|Newcastle-Upon-Tyne, England, United Kingdom, NE2 4HH|
|Principal Investigator:||Rachael Hough, MD||University College London Hospitals|