CD33KO-HSPC Infusion Followed by CART-33 Infusion(s) for Refractory/Relapsed AML

Inclusion criteria

• Male or female 18 years of age or older
• Subjects with AML unlikely to be cured with currently available therapies

• AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria; partial remission or refractory disease (including primary refractory) are eligible; OR:
• AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HCT is eligible; OR:
• Subjects with relapsed disease after prior transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment.
• Subjects must have a suitable stem cell donor.
• Satisfactory organ function

• Creatinine clearance > 40 ml/min
• ALT/AST must be ≤ 5x upper limit of normal unless related to disease and < 20 x upper limit of normal if related to disease
• Direct bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤ 3.0 mg/dL)
• Left ventricular ejection fraction ≥ 40% as confirmed by echocardiogram or MUGA
• DLCO > 45% predicted
• ECOG performance status 0-1
• Written informed consent is given
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion criteria

• Pregnant or lactating (nursing) women
• Active hepatitis B or hepatitis C or HIV infection
• Concurrent use of systemic steroids or immunosuppressant medications
• Any uncontrolled active medical disorder that would preclude participation as outlined
• Subjects with signs or symptoms indicative of CNS involvement.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
• Class III/IV cardiovascular disability according to New York Heart Association Classification
• Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the screening/enrollment visit.