Open Label NK Cell Infusion (FATE-NK100) With Subq IL-2 in Adults With AML

NCT03081780 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2016LS153
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I open-label dose escalation study of a single infusion of FATE-NK100 and a short course of subcutaneous interleukin-2 (IL-2) administered after lymphodepleting chemotherapy (CY/FLU) in subjects with refractory or relapsed acute myelogenous leukemia (AML). FATE-NK100 is a natural killer (NK) cell product that is enriched for NK cells with an "adaptive", or human cytomegalovirus (CMV)-induced, phenotype. The NK cell product is comprised of peripheral blood (PB) leukocytes sourced from a related donor (HLA-haploidentical or better but not fully HLA-matched) that is seropositive for cytomegalovirus (CMV+), and enriched for adaptive NK cells by depletion of CD3+ (T-lymphocytes) and CD19+ (B-lymphocytes) cells followed by ex-vivo culture expansion.

Conditions

Refractory Acute Myelogenous Leukemia; Relapsed Acute Myelogenous Leukemia

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Maximum FATE-NK100 dose which could be given to 3 participants such that not more than 1 participant experienced a DLT.

  3 months

Secondary Outcomes (8)

• Clinical activity by CR/CRp leukemia clearance

  Day +42

• Clinical activity by CR/CRp neutrophil recovery

  Day +42

• In vivo expansion of NK cells

  Day +14

• Treatment Related Mortality (TRM)

  6 months

• Minimal residual disease (MRD) by bone marrow morphology

  up to Day 28

Study Arms (1)

FATE NK-100

EXPERIMENTAL

Biological: FATE-NK100

Interventions

FATE-NK100 BIOLOGICAL

Preparative regimen: * Fludarabine 25 mg/m2 x 5 days start Day -6 * Cyclophosphamide 60 mg/kg x 2 days on Day -5 and -4 Apheresis cell collection (collected from the Donor Day - 8) will be enriched for FATE-NK100 per CMC. IL-2 at 6 million IU subcutaneously (SC) every other day (EOD) for 6 doses with Dose 1 on Day 0 (no sooner than 4 hours post NK cells) and last dose no later than Day +12.

FATE NK-100

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- ≥18 but ≤ 70 years of age
• Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease criteria:
• \* Primary induction failure:
• \*\* De Novo AML: no CR after 2, 3 or 4 induction attempts with high dose chemotherapy
• Secondary AML (from MDS or treatment related): no CR after 1, 2 or 3 cycles of high dose chemotherapy
• Relapsed:
• Not in CR after 1 or 2 cycles of standard re-induction therapy
• Relapse diagnosed at the time of the 6 months post-HCT standard of care follow-up or later (i.e. based on bone marrow biopsy performed Day +170 or later) and without evidence of graft versus host disease (GVHD)
• For patients \> 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required.
• Available HLA-matched or better but not fully HLA-matched (2/4 or 3/4 antigens) related donor (aged 18 to 75 years) with donor/recipient match based on a minimum of intermediate resolution DNA based Class I typing of the A and B locus who is CMV seropositive.
• Karnofsky Performance Status ≥ 60%
• Adequate organ function within 14 days of study registration (28 days for pulmonary and cardiac) defined as:
• Creatinine: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m\^2 per current institutional calculation formula
• Hepatic: AST and ALT ≤ 3 x upper limit of institutional normal
• Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if symptomatic or prior known impairment - must have pulmonary function \>50% corrected DLCO and FEV1

You may not qualify if:

• Myocardial Infraction (MI) within the previous 6 months
• Acute leukemias of ambiguous lineage
• Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test at screening
• History of or known active CNS involvement with AML
• Active autoimmune disease requiring systemic immunosuppressive therapy
• History of severe asthma and currently on chronic systemic medications (mild asthma requiring inhaled steroids only is eligible)
• New or progressive pulmonary infiltrates on screening chest X-ray or chest CT scan unless cleared for study by Pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
• Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
• Received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Murali Janakiram, MD, MS

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 16, 2017
• Study Start: April 27, 2017
• Primary Completion: August 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 12, 2021

Record last verified: 2021-03

Locations

US (1)