Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen
2 Years
60 Years
Both
Hematopoietic/Lymphoid Cancer
Trial Information
Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Non-relapse mortality at day 100
Safety Issue:
No
Principal Investigator
Rachael Hough, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University College London Hospitals
Authority:
Unspecified
Study ID:
CDR0000643641
NCT ID:
NCT00959231
Start Date:
January 2009
Completion Date:
Related Keywords:
- Hematopoietic/Lymphoid Cancer
- hematopoietic/lymphoid cancer
- Hematologic Diseases
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