Phase I/II Clinical Trial of Universal Donor CD33 CAR Natural Killer Cells for AML

Inclusion Criteria

• •1. Patients with relapsed or primary refractory CD33+ AML, including:
• •* Patients with relapsed AML (patients in second or subsequent relapse, or any relapse after HSCT, are eligible).
• •* Refractory AML defined as failure to achieve a complete response after 2 cycles of induction or reinduction chemotherapy, including persistent MRD positivity.
• •* Patients with isolated CNS or extramedullary disease are eligible. Patients with CNS disease are excluded from the phase I dose escalation portion but are eligible for the phase II portion of the study.
• •2. 1-39.99 years of age (note: the first three subjects treated AND the first subject on each dose level must be ≥ 16 years of age)
• •3. Negative serum test to rule out pregnancy within 14 days 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
• •4. Organ function requirements:
• •* Renal function: Creatinine ≤ 2 times the institutional upper limit of normal for age OR creatinine clearance \> 60 ml/min/1.73m2 (measured by 24 hour- urine specimen or radioisotope GFR)
• •* 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.
• •* Pulmonary function: baseline oxygen saturation \>92% on room air at rest
• •5. Due to the risk of hematopoietic toxicity from CD33 targeting, enrolled subjects must have an allogeneic HCT donor identified and be eligible and willing to undergo a subsequent HSCT in the event of aplasia.
• •6. All patients or their legal guardian must be able to understand and willing to sign a written informed consent document.
• •7. All patients must consent to enroll in a separate long term follow up study for cell and gene therapy