Universal Donor Natural Killer Cells for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia, KARMA Trial

Inclusion Criteria

• 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 central nervous system (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 * 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
• Creatinine ≤ 2 mg/dl OR creatinine clearance > 60 ml/min/1.73m^2
• Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome) * Upper limit of normal should be determined by the institutional defined normal laboratory range
• Aspartate aminotransferase (AST) and alanine aminotransferase (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
• Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal
• 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 principal investigator (PI) and/or co-investigators (Co-Is)
• All patients and/or their legal guardians must be able to understand and willing to sign a written informed consent document
• CRITERIA TO BEGIN CYCLE 2: Patients will be eligible to receive a second cycle of chemotherapy for the following reasons: * < CR or persistent MRD positivity after cycle 1 * Additional cycle is needed to bridge the patient to HSCT
• CRITERIA TO BEGIN CYCLE 2: ≥ 28 days since day 1 cycle 1
• CRITERIA TO BEGIN CYCLE 2: ≥ 48 hours since the last NK cell infusion in cycle 1
• CRITERIA TO BEGIN CYCLE 2: Bone marrow evaluation after cycle 1 complete
• CRITERIA TO BEGIN CYCLE 2: It is suggested but not required for ANC > 500/uL AND platelets > 50,000/uL prior to beginning cycle 2

Exclusion Criteria

• AML directed therapies in the 2 weeks prior to beginning treatment on this protocol (except for hydroxyurea) * Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
• Patients on immunosuppressive therapy * Patients must be off of all systemic immunosuppressive therapy for at least 2 weeks prior to enrollment with no evidence of recurrent graft versus host disease (GVHD)
• Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study
• Allogeneic stem cell transplantation (SCT) < 3 months prior to study enrollment
• Any comorbidities that in the opinion of the investigator will preclude receiving study therapy
• Performance status: Karnofsky or Lansky performance scale (PS) < 50
• Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy * Asymptomatic viremia such as cytomegalovirus (CMV), human papillomavirus (HPV), polyomavirus type BK (BK) virus, hepatitis C virus (HCV), etc. is NOT considered as an exclusion criterion
• Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
• History of autoimmune disease
• Active GVHD at the time of enrollment
• 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 (absolute neutrophil count [ANC] ≥ 500/μL, platelet count ≥ 50,000/μL)