Adapt NK for High Risk Myeloid Diseases as Bridge to Allo HSCT

Summary

This is a multi-institutional Phase I/II study of an allogeneic KIR-HLA mismatched NK cell infusion (AdaptNK) and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy \[cyclophosphamide (CY)/fludarabine (FLU)\] in patients with relapsed or refractory acute myelogenous leukemia (AML). AdaptNK is a natural killer (NK) cell product that is enriched for NK cells with an "adaptive", or human cytomegalovirus (CMV)-induced, phenotype.

Eligibility

Inclusion Criteria:

* 18-74 years with Karnofsky score ≥ 70%
* 75 years and older: KPS ≥ 70%, HCT-CI \< 5 (excluding history of solid tumor), AND not frail by Fried frailty criteria (see Appendix III)
* HLA type C1/C1 or C2/C2

Note: For easy determination, the definition of HLA-C ligand group assigments is included below:

HLA-C1 group alleles are defined as HLA-C01, C03, C07, C08, C12, C14, C16 HLA-C2 group alleles are defined as HLA-C02, C04, C05, C06, C15, C17, C18

* adequate liver, renal, pulmonary and cardiac function
* ability to be off glucocorticoids and other immunosuppressive medications indicated for acute or chronic GVHD for at least 28 days prior to the AdaptNK cell infusion
* There must be sufficient time between the most recent therapy and the screening bone marrow as delineated below:
* anti-leukemic systemic cytotoxic chemotherapy - 2 weeks
* Targeted anti-leukemic agents (FLT-3, IDH, menin inhibitors) - 3 half-lives of the medication
* Radiotherapy - 1 week
* donor lymphocyte infusions - 6 weeks
* hematopoietic growth factors (filgrastim, TPO agonists, EPO) - 1 week
* biologic therapy (monoclonal antibodies, T-cell engagers) - 2 weeks
* Immune effector cellular therapy - 4 weeks
* Intrathecal chemotherapy for treatment of active CNS leukemia - there must be at least two CSF samples negative for leukemia separated by one week before enrollment.
* WBC shall be \< 25,000 before infusion. Hydroxyurea is permitted until day -3 to control excess blast proliferation. No other systemic treatment is allowed after the screening bone marrow is performed for inclusion in protocol
* All prior treatment related toxicities should have resolved to ≤ grade 1 prior to study enrollment
* agrees to use of adequate contraception from study enrollment to 4 months after cell infusion
* voluntary written consent

Exclusion Criteria:

* Myeloid neoplasms with known or strongly suspected germline background, except DDX41, TP53, or RUNX1.
* Acute promyelocytic leukemia (APL)
* myocardial infarction (MI) within previous 6 months of study enrollment
* pregnant or breastfeeding
* Active CNS involvement with AML
* new or progressive pulmonary infiltrates
* active autoimmune disease requiring immunosuppressive therapy
* Preexisting inflammatory disease requiring immunosuppressive therapy
* history of severe asthma and currently on chronic systemic medications
* HIV-1/2 positivity or hepatitis C/B
* active systemic infections requiring anti-infective treatment
* received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)
* Patients with second malignancies are excluded if they have required systemic cytotoxic chemotherapy within 1 year or if they are not in remission
* Exception: patients that are on stable dosing of hormonal therapy (e.g. aromatase inhibitor or antiandrogen therapy) for active breast or prostate cancer for 1 year are eligible.
* Patients with excised basal cell or squamous cell carcinoma of the skin are eligible.
* Patients with excised carcinoma in situ of the cervix or breast are eligible.
* Patients with untreated T1a or T1b prostate cancer are eligible.

Conditions4

Interventions4

Locations1 site

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