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

Sponsor

Cancer Research UK (Other)

Overall Status

Unknown status

CT.gov ID

NCT00959231

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Masking:

None (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

Study Start Date :

Jan 1, 2009

Anticipated Primary Completion Date :

Aug 1, 2012

Outcome Measures

Primary Outcome Measures

Non-relapse mortality at day 100 []

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 []
Mixed chimerism []
Hemopoietic recovery []

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Bristol Royal Hospital for Children	Bristol	England	United Kingdom	BS2 8BJ
2	Cancer Research UK Clinical Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS16 6QB
3	University College of London Hospitals	London	England	United Kingdom	NW1 2PQ
4	UCL Cancer Institute	London	England	United Kingdom	WC1E 6DD
5	Great Ormond Street Hospital for Children	London	England	United Kingdom	WC1N 3JH
6	University of Newcastle-Upon-Tyne Northern Institute for Cancer Research	Newcastle-Upon-Tyne	England	United Kingdom	NE2 4HH