Patient case: 13-year-old male with acute myeloid leukemia; genetic feature: FLT3

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

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.


Eligibility: 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 *** 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 12 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 uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or 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
  Exclusion Criteria:
  -  Prior hematopoietic stem cell transplant for AM
  -  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)

Relevance to patient case: not relevant