Dysautonomia International

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

Purpose

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.

Conditions

Relapsed Adult AML
Refractory AML
Acute Myelogenous Leukemia

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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 Design

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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.

Recruiting Locations

Mark Juckett, MD
Minneapolis, Minnesota 55455

Contact:
Mark Juckett, MD
612-676-4200
juck0001@umn.edu

More Details

Status: Recruiting
Sponsor: Masonic Cancer Center, University of Minnesota

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.