Transduced T Cells (CART123) for the Treatment of Refractory or Relapsed Acute Myeloid Leukemia in Pediatric Patients

Inclusion Criteria

• Male and female patients >= 1 and =< 29 years of age at time of consent
• AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically: * Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR * Any detectable disease post-allogeneic transplant with flow cytometric confirmation (minimal residual disease [MRD]) of myeloid leukemia of at least 0.1%; OR * Refractory disease, defined as persistent bone marrow involvement with > 5% blasts after two courses of induction chemotherapy for patients at initial presentation or > 5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a complete response (CR)
• Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion
• A serum creatinine based on age/gender as follows: * 1 to < 2 years (age); 0.6 mg/dL (male) 0.6 mg/dL (female) * 2 to < 6 years (age); 0.8 mg/dL (male) 0.8 mg/dL (female) * 6 to < 10 years (age); 1.0 mg/dL (male) 1.0 mg/dL (female) * 10 to < 13 years (age); 1.2 mg/dL (male) 1.4 mg/dL (female) * 13 to < 16 years (age); 1.5 mg/dL (male) 1.4 mg/dL (female) * >= 16 years (age); 1.7 mg/dL (male) 1.4 mg/dL (female)
• Alanine aminotransferase (ALT) =< 5 x upper limit of normal (ULN)
• Total bilirubin =< 3 x ULN
• ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to AML infiltration of the liver
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea and < grade 3 hypoxia; carbon monoxide diffusing capability (DLCO) >= 40% (corrected for anemia) if pulmonary function test (PFTs) are clinically appropriate as determined by the treating investigator
• Left ventricular shortening fraction (LVSF) >= 28% or ejection fraction (LVEF) >= 45% confirmed by echocardiography (ECHO), or adequate ventricular function documented by a scan or a cardiologist. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice
• Adequate performance status defined as Lansky or Karnofsky score >= 50
• Signed informed consent must be obtained
• No contraindications for leukapheresis (unless apheresis product previously acquired)
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Pregnant or lactating (nursing) women
• Patients with relapsed AML with t(15:17)
• Patients < 6 months from alloHSCT
• Human immunodeficiency virus (HIV) infection
• Active hepatitis B or hepatitis C infection
• Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
• Concurrent use of systemic steroids at the time of cell infusion or cell collection or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well
• Any uncontrolled active medical disorder that would preclude participation as outlined
• Uncontrolled active infection
• Subjects with central nervous system leukemia (CNS3) disease that is progressive on therapy or with CNS parenchymal lesions that may increase the risk of CNS toxicity. Subjects with adequately treated CNS leukemia are eligible
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and Dextran 40)
• Patients with any prior history of myeloproliferative neoplasm
• Patients with somatic JAK2 V617F mutation by polymerase chain reaction (PCR) or next generation sequencing