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

ConditionsRelapsed Adult AML Refractory AML Acute Myelogenous Leukemia

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorMasonic Cancer Center, University of Minnesota

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

adequate liver, renal, pulmonary and cardiac function

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

AdaptNK
Biological/Vaccine
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.
Fludarabine
Drug
25 mg/kg administered on days -6, -5, -4, -3 and -2. Part of Lymphodepleting conditioning chemotherapy regimen.
Cyclophosphamide
Drug
60 mg/kg administered on days -5 and -4. Part of Lymphodepleting conditioning chemotherapy regimen.
IL-2
Drug
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.

Treatment groups

18 Participants

are divided into 4 treatment groups

Group A: Dose Level Cohort -1Experimental treatment 4 interventions

Group B: Dose Level Cohort 1Experimental treatment 4 interventions

Group C: Dose Level Cohort 2Experimental treatment 4 interventions

Group D: Dose Level Cohort 3Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

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.

Time frame

1 year

Secondary outcomes

Objective response (OR)

includes complete remission with or without hematologic recovery (CR or CRi) or partial remission (PR)

Time frame

Day 42

Safety of AdaptNK

measured by rate of treatment related mortality (TRM)

Time frame

Day 42

Other outcomes

Overall survival

Time frame

1 year

Overall survival

Time frame

2 year

Leukemia free survival (LFS)

Time frame

1 year

Leukemia free survival (LFS)

Time frame

2 year

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Masonic Cancer Center, University of Minnesota

Lead sponsor

Source ClinicalTrials.gov

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