CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploid Donor Natural Killer Cell Treatment in Older AML in First Complete Remission
NCT ID: NCT01639456
Last Updated: 2017-12-02
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE2
INTERVENTIONAL
2013-10-31
2017-01-31
Brief Summary
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Detailed Description
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Part 1: 1:1 randomization with 10 patients per cohort to either:
1. CD3-/CD19- NK cell product or
2. CD3-/CD56+ purified NK cell product The product with better NK cell expansion will be used for the rest of the trial. If the results and safety profile are equivalent, the CD56+ selection approach will be used. If neither approach results in successful NK cell expansion, the trial will be stopped and the platform redesigned.
Part 2: complete the trial by enrolling an additional 26 patients using the product deemed successful during part 1 to estimate the primary endpoint (DFS at 12 months)
Conditions
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Keywords
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Study Design
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RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Patients Using CD3-/CD19- NK cell product
Patients receive the apheresis product (collected day -1: enriched for NK cells using the CliniMACS® CD3 and CD19 Reagent System in combination with the large-scale tubing set (Miltenyi Biotec) to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19- natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.
CD3-/CD19- natural killer cells
Infused on Day 0. The final CD3-/CD19- product must contain at least 20% NK cells based on previous studies using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CliniMACS® CD3 and CD19 Reagent System
In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
Cyclophosphamide
Infused intravenously 60 mg/kg x day -5
Fludarabine
Fludarabine 25 mg/m2 x days -6 through -2
Aldesleukin
IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.
Patients Using CD3-/CD56+ purified NK cell product
Patients receive the apheresis product (collected day -1): purified for NK cells using the CliniMACS® CD3 Reagent System (Miltenyi Biotec) in combination with the large-scale tubing set to deplete CD3+ cells and then use the CliniMACS® CD56 Reagent System to enrich CD56+ NK cells (CD3-CD56+ natural killer cells). Patients will also receive Cyclophosphamide, Fludarabine and Aldesleukin.
CD3-CD56+ natural killer cells
Infused on Day 0. The final CD3-/CD56+ product must contain at least 70% NK cells based on a previous study using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CliniMACS® CD3 and CD19 Reagent System
In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CliniMACS® CD56 Reagent System
CliniMACS® CD3 and CD19 Reagent System will be used in addition to CliniMACS® CD56 Reagent System to enrich CD56+ NK cells. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
Cyclophosphamide
Infused intravenously 60 mg/kg x day -5
Fludarabine
Fludarabine 25 mg/m2 x days -6 through -2
Aldesleukin
IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.
Interventions
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CD3-/CD19- natural killer cells
Infused on Day 0. The final CD3-/CD19- product must contain at least 20% NK cells based on previous studies using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CD3-CD56+ natural killer cells
Infused on Day 0. The final CD3-/CD56+ product must contain at least 70% NK cells based on a previous study using this cell product processing technique. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CliniMACS® CD3 and CD19 Reagent System
In combination used to simultaneously deplete CD3+ cells to remove T-lymphocytes and deplete CD19+ cells to remove B-lymphocytes (CD3-/CD19-). The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
CliniMACS® CD56 Reagent System
CliniMACS® CD3 and CD19 Reagent System will be used in addition to CliniMACS® CD56 Reagent System to enrich CD56+ NK cells. The entire cell product will be administered except in cases where the T cell count exceeds the T cell infusion threshold. In such situations, the product volume will be adjusted to meet the lot release criteria.
Cyclophosphamide
Infused intravenously 60 mg/kg x day -5
Fludarabine
Fludarabine 25 mg/m2 x days -6 through -2
Aldesleukin
IL-2 subcutaneously at 6 million units every other day for 6 doses - begin evening of the NK cell infusion.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Meets the definition of complete remission by morphologic criteria including \<5% blasts in a moderately cellular (\> 20% cellularity) or cellular marrow.
* Complete remission (CR) was achieved after no more than 2 cycles of standard induction chemotherapy. Early re-induction therapy based on residual disease on a day 14 bone marrow (BM) will count as a 2nd cycle. Prior therapy with demethylating agents (i.e. azacitidine) is allowed, but patients must have attained CR after standard cytotoxic therapy (defined as absolute neutrophil count (ANC) \> 1000 cells/μL, platelets \> 100 x 10\^9/L)
* No more than 3 months have lapsed from attainment of CR1
* No acute myelogenous leukemia (AML) consolidation therapy administered prior to enrollment
* Not a candidate for allogeneic stem cell transplantation
* ≥ 60 years of age
* Karnofsky performance status ≥ 70%
* Available related HLA haploidentical natural killer (NK) cell donor (sibling, offspring, or offspring of an HLA identical sibling) by at least Class I serologic typing at the A\&B locus (donor age 18-75 years)
* At least 30 days since last dose of chemotherapy
* Adequate organ function within 14 days of enrollment defined as:
* Creatinine: ≤ 2.0 mg/dL
* Hepatic: aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) \< 5 x upper limit of institutional normal (ULN)
* Pulmonary: oxygen saturation ≥ 90% on room air
* Cardiac: left ventricular ejection fraction (LVEF) by echocardiogram (ECHO or MUGA) ≥ 40%, no uncontrolled angina, uncontrolled atrial or ventricular arrhythmias, or evidence of acute ischemia or active conduction system abnormalities (rate controlled a-fib is not an exclusion)
* Ability to be off prednisone and other immunosuppressive drugs for at least 3 days prior to the NK cell infusion (excluding preparative regimen pre-meds)
* Voluntary written consent
Exclusion Criteria
* New progressive pulmonary infiltrates on screening chest x-ray or chest Computed Tomography scan that has not been evaluated with bronchoscopy (when feasible). Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
* Uncontrolled bacterial, fungal, or viral infections including human immunodeficiency virus (HIV) - chronic asymptomatic viral hepatitis is allowed
* Pleural effusion large enough to be detectable on chest x-ray
* Known hypersensitivity to one or more of the study agents
Donor Selection:
* Related donor (sibling, offspring, or offspring of an HLA identical sibling) 18-75 years of age
* At least 40 kilograms
* In general good health as determined by the medical provider
* Negative for hepatitis and HIV on donor viral screen
* HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus
* Not pregnant
* Voluntary written consent
18 Years
75 Years
ALL
No
Sponsors
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Miltenyi Biomedicine GmbH
INDUSTRY
Masonic Cancer Center, University of Minnesota
OTHER
Responsible Party
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Principal Investigators
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Jeffrey S. Miller, M.D.
Role: PRINCIPAL_INVESTIGATOR
Masonic Cancer Center, University of Minnesota
Locations
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Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
Countries
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Other Identifiers
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MT2011-26
Identifier Type: OTHER
Identifier Source: secondary_id
2011LS151
Identifier Type: -
Identifier Source: org_study_id