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

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML Read More

Inclusion Criteria:

• Patients with relapsed or primary refractory AML, including:

  • Patients with relapsed AML after allogeneic stem cell transplantation
  • Isolated CNS or extramedullary disease
  • Primary refractory AML defined as failure to achieve a complete response (<5% BM blasts) after 2 cycles of induction chemotherapy
• Patient age 18-24.99 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

• 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 ≤ 150, and ALT ≤108 (unless related to leukemic involvement)
  • 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
• Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, stem cell transplant or radiotherapy prior to entering this study
• All prior treatment related toxicities must have resolved to ≤ Grade 2 prior to enrollment
• 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)

  • 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 GVHD
• Patients with a history of donor lymphocyte infusion 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 spontaneously or does not show evidence of significant resolution after initiating appropriate therapy

  • 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