- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01175785
Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies
Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells to Augment Single or Double Myeloablative Cord Blood Transplantation in Patients With Hematologic Malignancies
Study Overview
Status
Conditions
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
- Adult Acute Myeloid Leukemia With Del(5q)
- Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
- Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
- Adult Acute Myeloid Leukemia in Remission
- Childhood Acute Myeloid Leukemia in Remission
- Accelerated Phase Chronic Myelogenous Leukemia
- Childhood Acute Lymphoblastic Leukemia in Remission
- Childhood Chronic Myelogenous Leukemia
- Childhood Myelodysplastic Syndromes
- Chronic Phase Chronic Myelogenous Leukemia
- Previously Treated Myelodysplastic Syndromes
- Relapsing Chronic Myelogenous Leukemia
- Secondary Myelodysplastic Syndromes
- Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- de Novo Myelodysplastic Syndromes
- Refractory Anemia
- Refractory Anemia With Excess Blasts
- Refractory Anemia With Excess Blasts in Transformation
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Examine the safety and toxicity when ex vivo expanded cord blood cells are infused as an off-the-shelf non-human leukocyte antigen (HLA) matched product with the goal of providing rapid but transient myelopoiesis in the setting of a single or double umbilical cord blood transplant.
II. Examine the in vivo persistence of the ex vivo expanded cord blood product. The kinetics and durability of hematopoietic reconstitution will be determined and the relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment will be determined by frequent determination of donor chimerisms in the peripheral blood.
SECONDARY OBJECTIVES
I. Estimate the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients receiving off-the-shelf ex vivo expanded and cryopreserved cord blood cells.
II. Estimate the incidence of transplant related mortality at day 100.
III. Estimate the incidence of malignant relapse and probabilities of overall and event-free survival at 1 and 2 years post transplant.
IV. Obtain preliminary data on the incidence of infections/viral reactivation from the start of conditioning to 100 days post transplant and then at 6 months, 1 year and 2 years post transplant as possible.
V. Obtain preliminary data on the phenotype and function of immune cells recovering in patients receiving expanded and unmanipulated cord blood grafts.
VI. Examination of possible immunologic factors leading to emergence of a dominant unit.
OUTLINE:
MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total-body irradiation (TBI) twice daily on days -4 to -1.
TRANSPLANTATION: Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion.
GVHD PROPHYLAXIS: Patients initially receive cyclosporine (CSP) IV over 1 hour beginning on day -3. CSP may be given orally (PO) when the patient can tolerate oral medications and has a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive mycophenolate mofetil (MMF) IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later. If there is no evidence of acute GVHD and donor cluster of differentiation (CD)3 engraftment is at least 50% from one donor MMF may be tapered.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Acute myeloid leukemia:
- High risk complete response (CR)1 as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; >= 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, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment
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]
- Greater than 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 cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment
- Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate
- Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate 2 (Int-2) or high risk (i.e., refractory anemia with excess myeloblasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology
- Karnofsky (>= 16 years old) >= 70%
- Lansky (< 16 years old) >= 50%
- Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL (adults)
- Calculated creatinine clearance must be > 60 mL/min (children < 18 years old)
- Total serum bilirubin must be < 3 mg/dl
- Transaminases must be < 3 x the upper limit of normal
- Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 50% normal
- For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air
- Left ventricular ejection fraction > 45% OR shortening fraction > 26%
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Uncontrolled viral or bacterial infection at the time of study enrollment
- Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
- History of human immunodeficiency virus (HIV) infection
- Pregnant or breastfeeding
- If =< 18 years old, prior myeloablative transplant within the last 6 months
- If > 18 years old prior myeloablative allotransplant or autologous transplant
- Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (chemo, radiation, transplant, GVHD prophylaxis)
Patients receive fludarabine phosphate IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6.
Patients undergo TBI twice daily on days -4 to -1.
Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion.
Patients initially receive CSP IV over 1 hour beginning on day -3.
CSP may be given PO when the patient can tolerate oral medications and has a normal gastrointestinal transit time.
CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease.
Patients also receive MMF IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30.
MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later.
If there is no evidence of acute GVHD and donor CD3 engraftment is at least 50% from one donor MMF may be tapered.
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Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Undergo unmanipulated umbilical cord blood transplant
Other Names:
Undergo ex-vivo expanded cryopreserved cord blood progenitor cells
Other Names:
Given IV and PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1 year
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1 year
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Overall survival
Time Frame: 2 years
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2 years
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Event-free survival
Time Frame: 2 years
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2 years
|
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Event-free survival
Time Frame: 1 year
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1 year
|
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Time to neutrophil engraftment
Time Frame: By day 42
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Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) >= 500.
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By day 42
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Time to platelet engraftment
Time Frame: By day 100
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By day 100
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Overall survival
Time Frame: Day 100
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Day 100
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Overall survival
Time Frame: Day 180
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Day 180
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Event-free survival
Time Frame: Day 100
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Day 100
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Event-free survival
Time Frame: Day 180
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Day 180
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Incidence of severe (grades 3-4) acute GVHD
Time Frame: Up to day 100
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Up to day 100
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Incidence of grade greater than or equal to 3 infusional toxicity
Time Frame: By day 100
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Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
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By day 100
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Primary graft failure
Time Frame: By day 42
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Defined as failure to achieve ANC >= 500/mm^3 of donor origin.
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By day 42
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Secondary graft failure
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Precancerous Conditions
- Leukemia, Lymphoid
- Syndrome
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Anemia
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Leukemia, Myeloid, Accelerated Phase
- Anemia, Refractory, with Excess of Blasts
- Anemia, Refractory
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Cyclophosphamide
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- 2378.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2010-01426 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 2378
- RC2HL101844 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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