CAR T-cell therapy (ADCLEC.syn1) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Age >= 18 years of age at the time of signing informed consent
• Patients must have R/R AML. The following disease status will be eligible for the study: * Refractory AML is defined as failure to achieve a CR, complete remission with partial hematologic recovery (CRh) or CRi after one of the following regimens: ** At least one course of standard intensive induction chemotherapy (e.g., cytarabine plus anthraycline (7+3), mitoxantrone, etoposide, and cytarabine (MEC), high-dose cytarabine (HiDAC), etc.) or hypomethylating agent (HMA) or low dose cytarabine-based combination regimen including but not limited to venetoclax (e.g. venetoclax in combination with azacytidine, decitabine or cytarabine) ** Four cycles of HMA monotherapy * Relapsed AML is defined the appearance of >= 5% blasts in the bone marrow or peripheral blood at any time after achieving a CR, CRh, or CRi (i.e. first relapse and beyond)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Subjects must have a suitable stem cell donor identified who may donate cells in the event that the subject needs to undergo an allogeneic hematopoietic stem cell transplantation (HSCT) for rescue from prolonged marrow aplasia. Donor may be from related or unrelated matched source, haplo or cord, and must be found to be suitable according to the institution's standard criteria
• Serum creatinine < 2.0 mg/100 mL
• Total bilirubin < 2.0 mg/100 mL, unless benign congenital hyperbilirubinemia or due to leukemia organ involvement
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 5 × upper limit of normal (ULN), unless considered due to leukemic organ involvement

Exclusion Criteria

• Diagnosis of acute promyelocytic leukemia
• Radiologically-detected or symptomatic central nervous system (CNS) disease or CNS 3 disease (i.e., presence of >= 5/uL white blood cells (WBCs) in cerebrospinal fluid [CSF]). Subjects with adequately treated CNS leukemia are eligible
• Oxygen saturation < 90% on room air
• Patients with prior allogeneic HSCT are allowed as long as HSCT occurred > 3 months of signing informed consent form (ICF) and without ongoing requirement for systemic graft-versus-host therapy
• Treatment with clofarabine or cladribine within 3 months prior to leukapheresis
• The following medications are excluded: * Steroids: Therapeutic doses of corticosteroids (greater than 10mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CAR T cell infusion * Chemotherapy: Should be stopped one week prior to leukapheresis or starting conditioning chemotherapy. Hydroxyurea for cytoreduction can be administered up to 72 hours before leukapheresis or CAR T cell infusion
• Clinically significant cardiovascular disease, including stroke or myocardial infarction within 6 months prior to first study medication; or the presence of unstable angina or congestive heart failure of New York Heart Association grade 2 or higher; or cardiac ejection fraction < 50%
• Uncontrolled clinically significant infections such as ongoing fever for 48 hours, persistent bacteremia or requiring new supplemental oxygen
• Previous treatment with CAR therapy
• Positive serologic test results for HIV
• Acute or chronic hepatitis B virus (HBV) infection as assessed by serologic hepatitis B virus surface protein antigen (HBVsAg) or polymerase chain reaction (PCR) results, defined as HBVsAg+, hepatitis B virus core antibody positive (HBVcAb+), HBV PCR+
• Acute or chronic hepatitis C virus (HCV) infection as assessed by serologic hepatitis C virus antibody (HCV ab) or PCR results, defined as HCV Ab+ with reflex to positive HCV PCR
• Active second malignancy that requires systemic treatments, with the exception of malignancy treated with curative intent and without evidence of disease for > 2 years before screening
• Live vaccine within 4 weeks prior to leukapheresis
• Pregnant or lactating/breastfeeding women
• Any prior or ongoing condition/issue that in the opinion of the investigator would make the patient ineligible for study