Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Relapsed/Refractory AML

Prior treatment

• AML directed therapies in the 2 weeks prior to beginning treatment on this protocol (except for hydroxyurea)
  • o Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
• Patients on immunosuppressive therapy
  • o Patients must be off of all systemic immunosuppressive therapy for at least 2 weeks prior to enrollment with no evidence of recurrent GVHD
• Allogeneic SCT \< 3 months prior to study enrollment
• Any comorbidities that in the opinion of the investigator will preclude receiving study therapy

Other illness

• Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy
  • o Asymptomatic viremia such as CMV, HPV, BK virus, HCV, etc. is NOT considered as an exclusion criterion
• Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
• History of autoimmune disease

Lab values

• Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study
• Patients with a history of adoptive cell therapy are excluded unless at least 30 days from infusion and with evidence of recovery of normal hematopoiesis (ANC ≥ 500/μL, platelet count ≥ 50,000/μL).

Other

• Performance status: Karnofsky or Lansky Performance Scale (PS) \< 50
• Active GVHD at the time of enrollment

• Patients with relapsed or primary refractory AML, including:
  • Patients with relapsed AML (Any patient in first or subsequent relapse are eligible. Patients with relapse after HSCT are eligible)
  • Primary refractory AML defined as failure to achieve a complete response after 2 cycles of induction chemotherapy, including persistent MRD positivity
  • Patients with isolated CNS or extramedullary disease are eligible Note: a response monitoring plan must be developed a priori for subjects with extramedullary disease
• Patient age 1-24.99 years old
• Negative serum test to rule out pregnancy within 2 weeks prior to enrollment in females of childbearing potential
  • o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
• Negative serology for human immunodeficiency virus (HIV)
• Both males and females and members of all races and ethnic groups are eligible
• Organ function requirements:
  • Renal function: Creatinine ≤ 2 mg/dl OR creatinine clearance \> 60 ml/min/1.73m2.
  • Liver function: Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome), AST and ALT ≤ 5 times the upper limit of normal (unless related to leukemic involvement). Upper limit of normal should be determined by the institutional defined normal laboratory range.
  • Cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal.
  • CNS: Patients with seizure disorder may be eligible if seizures well controlled
• All prior treatment related non-hematologic toxicities must have resolved to ≤ Grade 2 prior to enrollment unless granted approval by study PI and/or Co-Is.
• All patients and/or their legal guardians must be able to understand and willing to sign a written informed consent document