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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00959231
First received: August 13, 2009
Last updated: August 23, 2013
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Hematopoietic/Lymphoid Cancer
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
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Non-relapse mortality at day 100 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 60
Study Start Date: January 2009
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   2 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00959231

Locations
United Kingdom
Bristol Royal Hospital for Children Recruiting
Bristol, England, United Kingdom, BS2 8BJ
Contact: Contact Person    44-117-342-8044      
Cancer Research UK Clinical Centre at St. James's University Hospital Recruiting
Leeds, England, United Kingdom, LS16 6QB
Contact: Contact Person    44-113-206-6020      
Great Ormond Street Hospital for Children Recruiting
London, England, United Kingdom, WC1N 3JH
Contact: Contact Person    44-207-813-8335      
UCL Cancer Institute Recruiting
London, England, United Kingdom, WC1E 6DD
Contact: Contact Person    44-207-830-2301      
University College of London Hospitals Recruiting
London, England, United Kingdom, NW1 2PQ
Contact: Rachael Hough, MD    44-845-155-5000 ext. 5239      
University of Newcastle-Upon-Tyne Northern Institute for Cancer Research Recruiting
Newcastle-Upon-Tyne, England, United Kingdom, NE2 4HH
Contact: Contact Person    44-191-222-7785      
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Rachael Hough, MD University College London Hospitals
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00959231     History of Changes
Other Study ID Numbers: CDR0000643641, CRUK-UCL-RIC-UCBT, EUDRACT-2004-003845-41, EU-20946
Study First Received: August 13, 2009
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
hematopoietic/lymphoid cancer

Additional relevant MeSH terms:
Hematologic Diseases
Cyclophosphamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Fludarabine monophosphate
Fludarabine
Mycophenolic Acid
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents

ClinicalTrials.gov processed this record on July 10, 2014