Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation
NCT ID: NCT02782546
Last Updated: 2025-12-24
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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ACTIVE_NOT_RECRUITING
PHASE2
60 participants
INTERVENTIONAL
2017-01-30
2028-02-13
Brief Summary
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A formal safety evaluation will be done after every 6th patient enrolled and the trial will be stopped if noted to have unusually higher engraftment failure (acute GVHD rates (\>60% any grades or \>30% grade III/IV or ≥ 50% severe cGVHD) or engraftment failure rates (≥15%).
Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Recipient
* Standard of care reduced conditioning regimen on Day -1
* Graft cell infusion on Day 0
* Post-transplant cyclophosphamide on Days +3 and +4
* GvHD prophylaxis with tacrolimus and mycophenolate mofetil (MMF) will start on Day +5. MMF will continue till Day +35 and tacrolimus till Day +180 in the absence of GvHD
* G-CSF will start on Day +7 and will continue until neutrophil engraftment as per institutional guidelines
* The cytokine-induced memory like natural killer (CIML NK) cells will be infused on Day +7 without a filter or pump, slowly by gravity over at least 15 minutes.
* ALT-803 will start approximately 4 hours after the CIML NK cell infusion. ALT-803 will be administered subcutaneously at a dose of 10 mcg/kg subcutaneously beginning Day +7 (on the day of CIML NK cell infusion) and then every 21 days for a total of 4 doses
Graft cell infusion
-Day 0
Tacrolimus
-GVHD prophylaxis
Mycophenolate mofetil
-GVHD prophylaxis
G-CSF
-Continue until neutrophil engraftment as per institutional guidelines
CIML NK cell infusion
-Day +7
ALT-803
-Start approximately 4 hours after CIML NK cell infusion
Donor
* Donors will receive subcutaneous G-CSF from Day -4 till Day 0 and undergo 20L apheresis per institutional guidelines.
* Two consecutive days for collection are allowed in case of the target CD34+ cell dose being less than the target 4 x106/kg-bw from the first day of collection.
* On Day +6 (one day before the planned CIML NK cell infusion), peripheral blood mononuclear cells will be collected by a single standard 20-L apheresis over 4-5 hours from the same haploidentical related donor that provided the HCT graft.
Leukapheresis
-Day +6
Interventions
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Graft cell infusion
-Day 0
Tacrolimus
-GVHD prophylaxis
Mycophenolate mofetil
-GVHD prophylaxis
G-CSF
-Continue until neutrophil engraftment as per institutional guidelines
CIML NK cell infusion
-Day +7
ALT-803
-Start approximately 4 hours after CIML NK cell infusion
Leukapheresis
-Day +6
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* At least 18 years of age
* Available HLA-haploidentical donor that meets the criteria in the protocol
* Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
* Karnofsky performance status \> 60 %
* Adequate organ function as defined below:
* Total bilirubin \< 2 mg/dl
* AST(SGOT)/ALT(SGPT) \< 3.0 x IULN
* Creatinine within normal institutional limits OR creatinine clearance \> 60 mL/min/1.73 m2 by Cockcroft-Gault Formula
* Oxygen saturation ≥90% on room air and adjusted DLCO of at least 40%
* Ejection fraction ≥40%
* Able to be off of corticosteroids (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) and any other immune suppressive medications beginning on Day -3
* Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
* Related donor (sibling, offspring, or offspring of sibling)
* At least 18 years of age
* HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus.
* In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
* Ability to understand and willingness to sign an IRB approved written informed consent document
Exclusion Criteria
* Circulating blast count \>30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed).
* Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
* Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of \>5000 as assessed by the single antigen bead assay, \< 6 weeks prior to starting transplant conditioning
* Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
* New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections)
* Known hypersensitivity to one or more of the study agents
* Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
* Pregnant and/or breastfeeding
* Positive for hepatitis, HTLV, or HIV infection
* Pregnant and/or breastfeeding
18 Years
ALL
No
Sponsors
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National Institutes of Health (NIH)
NIH
The V Foundation for Cancer Research
OTHER
National Cancer Institute (NCI)
NIH
ImmunityBio, Inc.
INDUSTRY
Washington University School of Medicine
OTHER
Responsible Party
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Principal Investigators
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Amanda Cashen, M.D.
Role: PRINCIPAL_INVESTIGATOR
Washington University School of Medicine
Locations
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Washington University School of Medicine
St Louis, Missouri, United States
Countries
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References
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Berrien-Elliott MM, Foltz JA, Russler-Germain DA, Neal CC, Tran J, Gang M, Wong P, Fisk B, Cubitt CC, Marin ND, Zhou AY, Jacobs MT, Foster M, Schappe T, McClain E, Kersting-Schadek S, Desai S, Pence P, Becker-Hapak M, Eisele J, Mosior M, Marsala L, Griffith OL, Griffith M, Khan SM, Spencer DH, DiPersio JF, Romee R, Uy GL, Abboud CN, Ghobadi A, Westervelt P, Stockerl-Goldstein K, Schroeder MA, Wan F, Lie WR, Soon-Shiong P, Petti AA, Cashen AF, Fehniger TA. Hematopoietic cell transplantation donor-derived memory-like NK cells functionally persist after transfer into patients with leukemia. Sci Transl Med. 2022 Feb 23;14(633):eabm1375. doi: 10.1126/scitranslmed.abm1375. Epub 2022 Feb 23.
Related Links
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Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Other Identifiers
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