Genetically Engineered Allogeneic Stem Cell Transplantation Followed by Chimeric Antigen Receptor T Cell Therapy for Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Male or female subjects 18 years of age or older
• Subjects with AML unlikely to be cured with currently available therapies. Specifically: * AML that has not achieved a complete remission or morphologic leukemia free state by European LeukemiaNet (ELN) criteria; partial remission or refractory disease (including primary refractory) are eligible; OR: * AML relapsed following allogeneic stem cell transplantation (including myelodysplastic syndrome [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 hematopoietic stem cell transplant (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. Donor may be matched or mismatched and must be found to be suitable according to the institution’s standard criteria; donors must agree to undergo one mobilized and one steady state apheresis
• Creatinine clearance > 40 ml/min
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) must be ≤ 5 x upper limit of normal unless related to disease and < 20 x upper limit of normal if related to disease
• Direct bilirubin < 2.0mg/dl, unless subject has Gilbert’s syndrome (≤ 3.0 mg/dL)
• Left ventricular ejection fraction ≥ 40% as confirmed by echocardiogram or MUGA
• Diffusion lung capacity of carbon monoxide (DLCO) > 45% predicted
• Eastern Cooperative Oncology Group (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. This study allows HIV with undetectable viral load, positive hepatitis B virus (HBV) serology with undetectable viral load and ongoing antiviral prophylaxis to prevent HBV reactivation, and positive hepatitis C virus (HCV) serology with quantitative polymerase chain reaction (PCR) for plasma HCV ribonucleic acid (RNA) below the lower limit of detection, with or without concurrent antiviral HCV treatment
• Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary
• Any uncontrolled active medical disorder that would preclude participation as outlined
• Subjects with signs or symptoms indicative of central nervous system (CNS) involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and Dextran 40)
• Class III/IV cardiovascular disability according to the 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