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

ClinicalTrials.gov ID NCT00959231
Sponsor Cancer Research UK
Information provided by National Cancer Institute (NCI)
Last Update Posted 2013-08-26
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Study Overview

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.

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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.

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Official Title
Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen
Conditions
Hematopoietic/Lymphoid Cancer
Intervention / Treatment
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: mycophenolate mofetil
    Other Study ID Numbers
    Study Start
    2009-01
    Primary Completion (Estimated)
    2012-08
    Enrollment (Estimated)
    60
    Study Type
    Interventional
    Phase
    Phase 2

    Participation Criteria

    Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

    For general information about clinical research, read Learn About Studies(https://clinicaltrials.gov/study-basics/learn-about-studies).
    Eligibility Criteria
    Description

    DISEASE CHARACTERISTICS:

    • Diagnosis of high-risk, advanced or poorly responding hematological disease for which a reduced-intensity hemopoietic stem cell transplantation is likely to be effective

      • Disease status is such that there is no alternative therapy likely to achieve a cure or provide a significant prolongation of disease-free survival
    • No chronic myelogenous leukemia in first chronic phase responding to imatinib or refractory blast crisis
    • No acute leukemia in morphological relapse/persistent disease (defined as > 5% blasts in normocellular bone marrow)
    • No malignant disease that is refractory to or progressive on salvage therapy
    • No myelofibrosis
    • Donor must be matched at HLA-A and -B at antigen level and HLA-DRB1 at allelic level

      • No available 5-6/6 HLA-A, -B, -DRB1 matched sibling donor OR 10/10 unrelated volunteer donor

    PATIENT CHARACTERISTICS:

    • Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100% (pediatrics)
    • Transaminases < 5 times upper limit of normal (ULN)
    • Bilirubin < 3 times ULN
    • Creatinine clearance > 50 mL/min
    • DLCO > 50% predicted
    • No supplemental oxygen requirements
    • Not pregnant or nursing
    • Negative pregnancy test
    • No HIV or HTLV (I and II) antibody positivity or evidence of infection
    • No acquired aplastic anemia
    • No decompensated congestive heart failure or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 35%
    • No current active serious infection, in particular uncontrolled fungal infection
    • No congenital immune deficiencies

    PRIOR CONCURRENT THERAPY:

    • See Disease Characteristics
    • More than 6 months since prior exposure to combination chemotherapy OR only 1 course of induction combination chemotherapy for myelodysplastic syndromes or acute myeloid leukemia (please discuss with study coordinator/s if this course contained fludarabine)
    • At least 6 months since prior myeloablative bone marrow transplantation
    • No prior irradiation that precludes the safe administration of an additional dose of 200 cGy of total-body irradiation
    • No prior autograft
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    Ages Eligible for Study
    2 Years to 60 Years (ChildAdult )
    Sexes Eligible for Study
    All
    Accepts Healthy Volunteers
    No

    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

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    Design Details
    Primary Purpose : Treatment
    Allocation : Non-Randomized
    Masking : None (Open Label)

    Arms and Interventions

    Intervention/Treatment
    Intervention/Treatment
    Drug: cyclophosphamide
    Drug: cyclosporine
    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
    Primary Outcome Measures
    Outcome Measure Measure Description Time Frame
    Non-relapse mortality at day 100 
    Secondary Outcome Measures
    Outcome Measure Measure Description Time Frame
    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 

    Collaborators and Investigators

    This is where you will find people and organizations involved with this study.
    Sponsor
    Cancer Research UK
    Investigators
    • Principal Investigator:Rachael Hough, MD,University College London Hospitals

    Publications

    From PubMed

    These publications come from PubMed, a public database of scientific and medical articles. This list is automatically created by ClinicalTrials.gov Identifier (NCT Number), and these articles may or may not be about the study.

    Study Record Dates

    These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
    Study Registration Dates
    First Submitted
    2009-08-13
    First Submitted that Met QC Criteria
    2009-08-13
    First Posted (Estimated)
    2009-08-14
    Study Record Updates
    Last Update Submitted that met QC Criteria
    2013-08-23
    Last Update Posted (Estimated)
    2013-08-26
    Last Verified
    2010-04

    More Information

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    Keywords Provided by National Cancer Institute (NCI)
    Additional Relevant MeSH Terms