Clinical trial NCT02782546: Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation
Official title: A Phase II Study of Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: The V Foundation for Cancer Research
name: National Cancer Institute (NCI)
name: ImmunityBio, Inc.
First posted: 2016-05-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a standard phase 2 study powered to demonstrate improvement in the 100 day leukemia free survival to 30% from \<10% expected with the use of reduced intensity haplo-HCT in this extremely high-risk patient cohort (based on the institutional experience using non-myeloablative / reduced intensity conditioning in a similar patient cohort).

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%).


Eligibility criteria: Recipient Inclusion Criteria:

* Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one or more cycles of re-induction therapy. Standard dose 10-day decitabine (20 mg/m2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy.
* 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).

Recipient Exclusion Criteria:

* Relapsed after allogeneic transplantation.
* 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

Donor Inclusion Criteria:

* 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

Donor Exclusion Criteria:

* Positive for hepatitis, HTLV, or HIV infection
* Pregnant and/or breastfeeding

Primary outcomes:
measure: Leukemia free survival rate (LFS)
timeFrame: 1 year post transplantation
Secondary outcomes:
measure: Leukemia free survival rate (LFS)
timeFrame: 3 months post transplantation
measure: Rate of overall survival (OS)
timeFrame: 1 year post transplantation
measure: Incidence of relapse in patients who are found to be CR (complete remission)
timeFrame: Day 28 post transplantation
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Amanda Cashen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.