Killer Cells Against Relapsed/Refractory Myeloid Acute Leukemia (KARMA): a Clinical Trial Evaluating the Safety and Efficacy of Expanded, Universal Donor Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Description

This is a phase I/II dose escalation study designed to determine the safety and estimate the efficacy of UD-NK cells combined with FLA chemotherapy in patients age 1-24.99 with relapsed or refractory acute myeloid leukemia. PRIMARY OBJECTIVE: I. To determine the safety and recommended phase II dose of adoptive NK cell therapy using UD-NK cells in pediatric and young adult patients with relapsed/refractory AML. SECONDARY OBJECTIVES: I. To estimate the efficacy of UD- NK cells with FLA chemotherapy in pediatric and young adult patients with relapsed/refractory AML. EXPLORATORY OBJECTIVES: I. To determine the immunophenotype and function of UD-NK cells II. To characterize in vivo expansion of UD-NK cells III. To determine the persistence of UD-NK cells Six doses of universal donor mbIL-21 expanded NK cells (UD-NK) given thrice weekly for two weeks. Days may vary and NK cells can be given from days 0 to 21. Patients may receive up to 2 cycles of fludarabine/cytarabine (FLA) + NK c

Trial Eligibility

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 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 Exclusion Criteria: * 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 * Patients with a history of donor lymphocyte infusion or cellular therapy within the last 30 days are not eligible for this study * Allogeneic 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 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 * 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 (ANC ≥ 500/μL, platelet count ≥ 50,000/μL).

Study Info

Interventions

Locations Recruiting

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