Hematopoietic/Lymphoid CancerPhase 2NCT00959231
Donor Umbilical Cord Blood Transplant After Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease
A Phase 2 study testing cyclophosphamide, cyclosporine and fludarabine phosphate in people with Hematopoietic/Lymphoid Cancer, run by Cancer Research UK at 6 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 60 years
- Conditions the study is for
- Hematopoietic/Lymphoid Cancer
- What is being tested?
- cyclophosphamide, cyclosporine and fludarabine phosphate
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- Jan 2009to Aug 2012
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites, 6 recruiting
- Recruiting
Bristol Royal Hospital for Children
Bristol, England, BS2 8BJ
Contact Person, 44-117-342-8044
- Recruiting
Cancer Research UK Clinical Centre at St. James's University Hospital
Leeds, England, LS16 6QB
Contact Person, 44-113-206-6020
- Recruiting
University College of London Hospitals
London, England, NW1 2PQ
Rachael Hough, MD, 44-845-155-5000 ext. 5239
- Recruiting
UCL Cancer Institute
London, England, WC1E 6DD
Contact Person, 44-207-830-2301
- Recruiting
Great Ormond Street Hospital for Children
London, England, WC1N 3JH
Contact Person, 44-207-813-8335
- Recruiting
University of Newcastle-Upon-Tyne Northern Institute for Cancer Research
Newcastle upon Tyne, England, NE2 4HH
Contact Person, 44-191-222-7785
About this study
Official title: Transplantation of Umbilical Cord Blood From Unrelated Donors in Patients With Haematological Diseases Using a Reduced Intensity Conditioning Regimen
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.
Read the 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.
- Conditions
- Hematopoietic/Lymphoid Cancer
- Being tested
- cyclophosphamide, cyclosporine, fludarabine phosphate, mycophenolate mofetil, laboratory biomarker analysis
- Keywords
- hematopoietic/lymphoid cancer
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
cyclosporineDrug
laboratory biomarker analysisOther
nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery
umbilical cord blood transplantationProcedure or surgery
total-body irradiationRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-relapse mortality at day 100
Secondary outcomes (3)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2009 (estimated)
- Study startJan 2009
- Primary completionAug 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematopoietic/Lymphoid CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Investigators
- Rachael Hough, MD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00959231
- Sponsor's protocol ID
- CDR0000643641
- Other IDs
- CRUK-UCL-RIC-UCBT, EUDRACT-2004-003845-41, EU-20946
- Status last verified
- Apr 2010
- First submitted
- 13 Aug 2009
- Last updated
- 26 Aug 2013
- Results posted
- No
Publications
Hough R, Lopes A, Patrick P, Russell N, Raj K, Tholouli E, A Snowden J, Collin M, El-Mehidi N, Lawrie A, Clifton-Hadley L, Veys P, Craddock C, Mackinnon S, Cook G, Shaw B, Marks D. Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation. Blood Adv. 2022 Apr 12;6(7):2414-2426. doi: 10.1182/bloodadvances.2021005106.
PubMed 34700343