A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies
5 other identifiers
interventional
23
1 country
4
Brief Summary
This phase I multicenter feasibility trial is studying the safety and potential efficacy of infusing ex vivo expanded cord blood progenitors with one unmanipulated umbilical cord blood unit for transplantation following conditioning with fludarabine, cyclophosphamide and total body irradiation (TBI), and immunosuppression with cyclosporine and mycophenolate mofetil (MMF) for patients with hematologic malignancies. Chemotherapy, such as fludarabine and cyclophosphamide, and TBI given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts are more likely to recover more quickly if increased numbers of cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one unexpanded cord blood unit is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two cord blood units makes up the patient's new blood system, and how quickly immune system cells return
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2006
CompletedFirst Submitted
Initial submission to the registry
June 22, 2006
CompletedFirst Posted
Study publicly available on registry
June 23, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2013
CompletedFebruary 11, 2015
February 1, 2015
7.3 years
June 22, 2006
February 10, 2015
Conditions
Outcome Measures
Primary Outcomes (3)
Severe (grades 3 and 4) acute GVHD
Up to day 100
Grade greater than or equal to 3 infusional toxicity
Day 0
Graft failure as defined by failure to achieve ANC greater than or equal to 500/mm^3 of donor origin
By day +42
Study Arms (1)
Treatment (umbilical cord blood transplant)
EXPERIMENTALMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. TRANSPLANTATION : Patients undergo double-unit umbilical cord blood transplantation comprising unmanipulated umbilical cord blood unit IV over 20-30 minutes, and 4-6 hours later patients receive ex vivo-expanded umbilical cord blood cells IV over 30 minutes on day 0. GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients receive cyclosporine IV every 8 or 12 hours on days -3 to 100, followed by a taper to at least day 180. Patients also receive MMF IV every 8 hours on days -3 to 5 and then PO, if tolerated, on days 6-30.
Interventions
Given IV
Given IV
Given IV
Given IV or PO
Undergo double-unit umbilical cord blood transplantation
Undergo double-unit umbilical cord blood transplantation
Optional correlative studies
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- Patient has no existing 0-1 HLA-A, B, C, DRB1 and DQB1 matched related donor
- Acute Myeloid Leukemia:
- High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or HR as defined by referring institution treatment protocol), \>= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; \>= second complete remission (CR2);
- All patients must be in CR as defined by hematologic recovery and \< 5% blasts by morphology within the bone marrow and a cellularity of \>= 15%;
- Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (\< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
- Acute lymphoblastic leukemia:
- High risk CR1 (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia (MLL) rearrangements, hypodiploid);
- \> 1 cycle to obtain CR;
- \>= CR2;
- All patients must be in CR as defined by hematologic recovery and \< 5% blasts by morphology within the bone marrow and a cellularity of \>= 15%;
- Patients in which adequate marrow/biopsy specimens can not be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (\< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
- Chronic Myelogenous Leukemia:
- Patients in blast crisis (BC) must receive therapy and must achieve accelerated phase (AP)/chronic phase (CP) in order to be eligible (patients who remain in BC are not eligible);
- If in first chronic phase, patient must have failed or be intolerant to imatinib mesylate
- Myelodysplasia (MDS):
- +14 more criteria
You may not qualify if:
- Acute leukemia in relapse (\>= 5% marrow blasts by morphology)
- Active central nervous system (CNS) leukemia involvement at the time of study enrollment (cerebrospinal fluid with \> 5 white blood cells (WBC)/mm\^3 AND malignant cells on cytospin)
- Chemotherapy refractory large cell lymphoma and high grade NHL (progressive disease after \> 2 salvage regimens)
- Female patients who are pregnant or breastfeeding
- Karnofsky performance status \< 70% (adults) or Lanksy score \< 50% (pediatrics)
- Prior autologous or allogeneic stem cell transplant with myeloablative preparative regimen (If =\< 18 years old, prior myeloablative transplant within the last 6 months)
- Uncontrolled viral, or bacterial infection at the time of study enrollment
- Active or recent (prior 6 months) invasive fungal infection without ID consult and approval
- Seropositive for human immunodeficiency virus (HIV)
- Consenting 5 of 6 or 6 of 6 HLA-matched related donor available
- Unable to provide informed consent
- Use of any other experimental drug within 28 days of baseline
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
- Damon Runyon Cancer Research Foundationcollaborator
Study Sites (4)
City of Hope Medical Center
Duarte, California, 91010, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, 80045, United States
University of Colorado
Denver, Colorado, 80217-3364, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Colleen Delaney
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 22, 2006
First Posted
June 23, 2006
Study Start
April 1, 2006
Primary Completion
July 1, 2013
Last Updated
February 11, 2015
Record last verified: 2015-02