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

Safety and Efficacy of Expanded KIR-HLA Mismatched Natural Killer Cell Immunotherapy (AdaptNK) for High-Risk Myeloid Diseases as Bridge to Allogeneic Hematopoietic Stem Cell Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myelogenous Leukemia; Relapsed Adult AML; Refractory AML
• Intervention / Treatment: Biological: AdaptNK; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: IL-2

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Mark Juckett, MD
      • Contact: Mark Juckett, MD; Phone Number: 612-676-4200; Email: juck0001@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level Cohort -1; Safety dose level. < 1 x 10^8 Total Nucleated Cells (TNC) of AdaptNK product administered intravenously (IV).	Biological: AdaptNK; The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a cryopreserved pool. of third-party donors that are seropositive for cytomegalovirus (CMV+), have NK cells expressing >20% NKG2C and >30% single-self KIR and depleted from CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells.; Drug: Fludarabine; 25 mg/kg administered on days -6, -5, -4, -3 and -2. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: Cyclophosphamide; 60 mg/kg administered on days -5 and -4. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: IL-2; IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 3 doses with Dose 1 on Day 0 (no sooner than 4 hours post cell infusion) with the last dose no later than Day +8.
Experimental: Dose Level Cohort 1; 2.4 - 3 x 10^8 Total Nucleated Cells (TNC) of AdaptNK product administered intravenously (IV).	Biological: AdaptNK; The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a cryopreserved pool. of third-party donors that are seropositive for cytomegalovirus (CMV+), have NK cells expressing >20% NKG2C and >30% single-self KIR and depleted from CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells.; Drug: Fludarabine; 25 mg/kg administered on days -6, -5, -4, -3 and -2. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: Cyclophosphamide; 60 mg/kg administered on days -5 and -4. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: IL-2; IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 3 doses with Dose 1 on Day 0 (no sooner than 4 hours post cell infusion) with the last dose no later than Day +8.
Experimental: Dose Level Cohort 2; 0.8 - 1 x 10^9 Total Nucleated Cells (TNC) of AdaptNK product administered intravenously (IV).	Biological: AdaptNK; The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a cryopreserved pool. of third-party donors that are seropositive for cytomegalovirus (CMV+), have NK cells expressing >20% NKG2C and >30% single-self KIR and depleted from CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells.; Drug: Fludarabine; 25 mg/kg administered on days -6, -5, -4, -3 and -2. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: Cyclophosphamide; 60 mg/kg administered on days -5 and -4. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: IL-2; IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 3 doses with Dose 1 on Day 0 (no sooner than 4 hours post cell infusion) with the last dose no later than Day +8.
Experimental: Dose Level Cohort 3; 2.4 - 3 x 10^9 Total Nucleated Cells (TNC) of AdaptNK product administered intravenously (IV).	Biological: AdaptNK; The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a cryopreserved pool. of third-party donors that are seropositive for cytomegalovirus (CMV+), have NK cells expressing >20% NKG2C and >30% single-self KIR and depleted from CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells.; Drug: Fludarabine; 25 mg/kg administered on days -6, -5, -4, -3 and -2. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: Cyclophosphamide; 60 mg/kg administered on days -5 and -4. Part of Lymphodepleting conditioning chemotherapy regimen.; Drug: IL-2; IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 3 doses with Dose 1 on Day 0 (no sooner than 4 hours post cell infusion) with the last dose no later than Day +8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	The primary objective of the study is to assess the safety and determine the maximum tolerated dose (MTD) of AdaptNK administered as a single infusion intravenously (IV) to KIR-HLA mismatched patients with relapsed or refractory AML.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response (OR)	includes complete remission with or without hematologic recovery (CR or CRi) or partial remission (PR)	Day 42
Safety of AdaptNK	measured by rate of treatment related mortality (TRM)	Day 42

Other Outcome Measures

Outcome Measure	Time Frame
Overall survival	1 year
Overall survival	2 year
Leukemia free survival (LFS)	1 year
Leukemia free survival (LFS)	2 year

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2035

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukins; Lymphokines; Cyclophosphamide; Interleukin-2; fludarabine
• Other Study ID Numbers: 2023LS005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No