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 criteria109; 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 a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the screening/enrollment visit.