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Donor Umbilical Cord Blood Transplant After Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease

Phase 2
Conditions
Hematopoietic/Lymphoid Cancer
Registration Number
NCT00959231
Lead Sponsor
Cancer Research UK
Brief Summary

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.

Detailed Description

OBJECTIVES:

* 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Non-relapse mortality at day 100
Secondary Outcome Measures
NameTimeMethod
Incidence of grades II-IV and III-IV acute graft-vs-host disease (GVHD) at day 100 and chronic GVHD at 1 year
Mixed chimerism
Hemopoietic recovery

Trial Locations

Locations (6)

Great Ormond Street Hospital for Children

🇬🇧

London, England, United Kingdom

UCL Cancer Institute

🇬🇧

London, England, United Kingdom

Bristol Royal Hospital for Children

🇬🇧

Bristol, England, United Kingdom

University of Newcastle-Upon-Tyne Northern Institute for Cancer Research

🇬🇧

Newcastle-Upon-Tyne, England, United Kingdom

University College of London Hospitals

🇬🇧

London, England, United Kingdom

Cancer Research UK Clinical Centre at St. James's University Hospital

🇬🇧

Leeds, England, United Kingdom

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