CART123 with and without Ruxolitinib for the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Age at time of consent: * Cohort A: 0-29 years * Cohort B: 1-29 years (Note: the first subject at each dose level of Cohort B must be ≥ 12 years old)
• Subjects with AML in second or greater relapse, post-transplant relapse, or with chemotherapy-refractory disease. Specifically: * Second or greater relapse defined as bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy after second documented complete remission; OR * Any detectable disease post-allogeneic transplant with bone marrow flow cytometric confirmation of myeloid leukemia of at least 0.1% or development of extramedullary disease by imaging or biopsy; OR * Refractory disease, defined as: ** Persistent bone marrow involvement with ≥ 0.1% disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after two courses of induction chemotherapy for patients at initial presentation ** ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of induction chemotherapy for patients who have relapsed after previously achieving a complete remission (CR) ** ≥ 0.1% bone marrow disease by flow cytometry or persistent extramedullary disease by imaging or biopsy after one course of AML-directed chemotherapy for those with myeloid lineage switch
• Subjects must have an identified stem cell donor with the ability to proceed rapidly to transplant following CART123 treatment if indicated
• Serum creatinine based on age/gender as follows: * Age: 0 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male); 0.6 (female) * Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male); 0.8 (female) * Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1.0 (male); 1.0 (female) * Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female) * Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female) * Age: ≥ 16 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
• Alanine aminotransferase (ALT) ≤ 500 U/L * 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
• Bilirubin ≤ 3 x the upper limit of normal * 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; diffusing capacity for carbon monoxide (DLCO) ≥ 40% (corrected for anemia if necessary) if pulmonary functions tests (PFTs) are clinically appropriate as determined by the treating investigator
• Left ventricular shortening fraction (LVSF) ≥ 28% or ejection fraction (LVEF) ≥ 45% confirmed by echocardiogram or another scan
• Adequate performance status defined as Lansky or Karnofsky performance score ≥ 50
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Active hepatitis B or active hepatitis C
• HIV infection
• Active acute or chronic graft versus host disease (GVHD) requiring systemic therapy
• Concurrent use of systemic steroids or immunosuppression 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 or immunosuppression 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
• Central nervous system (CNS) disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
• Pregnant or nursing (lactating) subjects
• Uncontrolled active infection