CART123 Cells in Treating Patients with Refractory or Relapsed Acute Myeloid Leukemia

Inclusion Criteria

• Subjects with active acute myeloid leukemia (AML) with no available curative treatment options using 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, minimal residual disease [MRD]) at any time after allogeneic hematopoietic cell transplantation (HCT) is eligible.
• Subjects with relapsed disease after prior transplant must meet one of the following: * Subjects with relapsed disease after prior allogeneic HCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and ** Have no residual donor cells (by short tandem repeat [STR] analysis on 2 occasions separated by at least 1 month), OR: ** Donor cells are present but there is no active graft versus host disease (GVHD) (> grade [Gr] II), subject does not require systemic immunosuppression and is more than 3 months from transplant, and at least 1 month off GVHD prophylaxis. * Subjects with relapsed disease after prior autologous or syngeneic HCT will be eligible if they meet all other inclusion criteria and it has been more than 3 months from transplant.
• Subjects must have a suitable stem cell donor available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution’s standard criteria; donors must be fully cleared to proceed as the donor.
• Creatinine =< 1.6 mg/dl.
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) must be =< 5 x upper limit of normal unless related to disease.
• Direct bilirubin or total bilirubin < 2.0 mg/dl, unless subject has Gilbert’s syndrome (=< 3.0 mg/dL).
• Left ventricular ejection fraction >= 40% as confirmed by echocardiography (ECHO)/multigated acquisition scan (MUGA).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Written informed consent is given.
• No contraindications for leukapheresis.
• Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion Criteria

• Pregnant or lactating (nursing women) women.
• Patients with relapsed AML with t(15:17).
• Human immunodeficiency virus (HIV) infection.
• Active hepatitis B or hepatitis C infection.
• 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.
• Patients 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.