FATE-NK100 Donor Natural Killer Cells, Aldesleukin, and Combination Chemotherapy in Treating Patients with Refractory or Relapsed Acute Myeloid Leukemia
- 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 myelodysplastic syndrome [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 *** For patients > 60 years of age, the minimum of 1 cycle of standard chemotherapy is not required ** Relapse diagnosed at the time of the 6 months post-hematopoietic cell transplantation (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) * Notes: ** For hypomethylating agents (i.e. decitabine, azacititdine) to count as an induction/re-induction attempt, the patient must have completed a minimum of 3 monthly cycles ** For targeting agents (i.e. sorafenib) to count as an induction/re-induction attempt, the patient must have completed a minimum of 1 month without attaining CR ** 7+3 followed by 5+2 counts as TWO induction attempts ** Use of hydroxyurea is permitted to control blasts until day -3
- Available human leukocyte antigen (HLA)-haploidentical 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 deoxyribonucleic acid (DNA) based class I typing of the A and B locus who is CMV seropositive
- Karnofsky Performance Status >= 60%
- Estimated glomerular filtration rate (eGFR) >= 50 mL/min/1.73m^2 per current institutional calculation formula (within 14 days of study registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of institutional normal (within 14 days of study registration)
- Oxygen saturation >= 90% on room air; pulmonary function tests (PFT’s) required only if symptomatic or prior known impairment - must have pulmonary function > 50% corrected diffusion capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume in 1 second (FEV1) (within 28 days of study registration)
- Left ventricular ejection fraction (LVEF) >= 40% by echocardiography or multi-gated acquisition scan (MUGA) or cardiac magnetic resonance imaging (MRI) (within 28 days of study registration)
- No symptomatic active conduction system abnormalities (within 28 days of study registration)
- Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to FATE-NK100 cell infusion (excluding preparative regimen pre-medications)
- 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
- DONOR ELIGIBILITY REQUIREMENTS: HLA-haploidentical or better but not fully HLA-matched 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 (2/4 or 3/4 class I allele) (determined during pre-screening)
- DONOR ELIGIBILITY REQUIREMENTS: Seropositive for cytomegalovirus (CMV+) as determined during pre-screening
- DONOR ELIGIBILITY REQUIREMENTS: Body weight of at least 40 kilograms
- DONOR ELIGIBILITY REQUIREMENTS: In general good health as determined by the medical provider
- DONOR ELIGIBILITY REQUIREMENTS: Hemoglobin within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
- DONOR ELIGIBILITY REQUIREMENTS: White blood cell (WBC) within 10% of upper and lower limit of normal range of test
- DONOR ELIGIBILITY REQUIREMENTS: Platelet within 10% of upper and lower limit of normal range of test
- DONOR ELIGIBILITY REQUIREMENTS: Alanine aminotransferase (ALT) < 2 x upper limit of normal
- DONOR ELIGIBILITY REQUIREMENTS: Serum creatinine < 1.8 mg/dl
- DONOR ELIGIBILITY REQUIREMENTS: Performance of a donor infectious disease screen panel including CMV antibody, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, HIV 1/2 antibody, human T-lymphotropic virus antibody (HTLVA) 1/2 antibody, Treponema and Trypanosoma cruzi (T. cruzi) plus hepatitis B virus (HBV), hepatitis C virus (HCV), West Nile virus (WNV), HIV by nucleic acid method, and risk assessment for Zika virus exposure or per current standard institutional donor screen – must be negative for HIV and active hepatitis B
- DONOR ELIGIBILITY REQUIREMENTS: Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of apheresis
- DONOR ELIGIBILITY REQUIREMENTS: Voluntary written consent prior to the performance of any research related procedure
- Myocardial Infraction (MI) within the previous 6 months
- Acute leukemias of ambiguous lineage
- Pregnant or breastfeeding; women of child bearing potential must have a negative pregnancy test at screening
- History of or known active central nervous system (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 computed tomography (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 human immunodeficiency virus (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 phosphate [fludarabine])
I. To assess the safety and determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of allogeneic CD3- CD19- CD57+ NKG2C+ NK cells FATE-NK100 (FATE-NK100) administered intravenously (IV) in patients with refractory or relapsed acute myeloid leukemia (AML).
I. To assess clinical activity by complete remission/complete remission with incomplete platelet recovery (CR/CRp) at 42 days where CR is defined as =< 5% blasts in the bone marrow (BM), recovery of neutrophils and platelets, and the absence of extramedullary disease and CRp is defined as leukemia clearance (=< 5% marrow blasts and no circulating peripheral blasts) and neutrophil recovery but with incomplete platelet recovery.
II. To determine the incidence of in vivo expansion (>= 100 donor derived NK cells per uL blood) of NK cells by day +7 and day +14.
III. To evaluate the safety of FATE-NK100 as measured by rate of treatment related mortality (TRM) at 6 months.
IV. To evaluate the rate of minimal residual disease (MRD) clearance.
V. To measure leukemia free survival (LFS) and overall survival (OS) at 1 year.
I. To measure function of in vivo expanded adoptively transferred FATE-NK100.
II. To correlate CR/CRp with in vivo expansion of FATE-NK100.
OUTLINE: This is a dose-escalation study of FATE-NK100.
Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 2 hours on days -5 and -4. Patients then receive FATE-NK100 IV over 15 minutes to 1 hour on day 0 and aldesleukin subcutaneously (SC) every other day (QOD) on days 0-10.
After completion of study treatment, patients are followed up at 2, 3, 6, and 12 months.
Trial Phase Phase I
Trial Type Treatment
University of Minnesota / Masonic Cancer Center
- Primary ID 2016LS153
- Secondary IDs NCI-2017-01462
- Clinicaltrials.gov ID NCT03081780