Adapt NK cells for high-risk AML bridging to stem cell transplant

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multi-institutional Phase I/II trial evaluating AdaptNK, an NK cell product enriched for adaptive CMV-induced NK cells, given after lymphodepleting chemotherapy (cyclophosphamide/fludarabine) followed by a short course of subcutaneous IL-2. Participants have relapsed or refractory acute myeloid leukemia and are eligible based on age, performance status, organ function, and HLA-C1/C1 or C2/C2 status. The study aims to determine safety and preliminary effectiveness as a bridging therapy to allogeneic HSCT. The intervention comprises AdaptNK cell infusions in combination with the lymphodepleting regimen and post-infusion IL-2 support, with careful timing relative to prior therapies and donor availability.

Why it matters

Who can join: the full rules

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.

Where it's running

• Mark Juckett, MD
  Minneapolis, Minnesota, United States Recruiting

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.