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

University of Minnesota (UMN)

Status and phase

Completed

Phase 1

Conditions

Relapsed Acute Myelogenous Leukemia

Refractory Acute Myelogenous Leukemia

Treatments

Biological: FATE-NK100

Study type

Interventional

Funder types

Other

Identifiers

NCT03081780

2016LS153

Details and patient eligibility

About

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.

Enrollment

6 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

≥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
- Cardiac Function: LVEF ≥ 40% by echocardiography or MUGA
- No symptomatic active conduction system abnormalities
Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to FATE-NK100 cell infusion (excluding preparative regimen premedications)
Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
Voluntary written consent prior to the performance of any research related procedures

Arm Specific Inclusion Criteria

High-Risk aGVHD (ARM 1):

Pediatric or adult (ages 0-76 years) HCT recipients with high-risk acute GVHD, as determined either by the refined MN acute GVHD risk score [28]: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3) [31]. Patients in this arm must start treatment within the first 7 days after onset of high-risk aGVHD.

Steroid- Dependent aGVHD (ARM 2A):

Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid-dependent acute GVHD, defined as any one of the following: Flare of acute GVHD of at least grade II/IV severity within 8 weeks of tapering down or (off of) immunosuppression for acute GVHD, with the flare occurring on ≤0.5 mg/kg prednisone. This can include late-onset aGVHD and overlap syndrome.

Steroid-Refractory aGVHD (ARM 2B):

Pediatric or adult (ages 0-76 years) HCT recipient with grade II-IV steroid refractory acute GVHD, defined as any one of the following:

No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
Flare of acute GVHD of at least grade II/IV severity while on steroids at a dose >0.5/mg/kg/day. This can include late-onset aGVHD and overlap syndrome.

Exclusion criteria

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)