Genetically Modified Cells (CART19) for the Treatment of Pediatric B cell Acute Lymphoblastic Leukemia

Inclusion Criteria

• Signed informed consent form must be obtained prior to any study procedure
• Patients with documented CD19+ B cell acute lymphoblastic leukemia (B-ALL) * Cohort A & B: Patients, regardless their response to initial or relapsed B ALL therapy, with the following characteristics: ** Cohort A: Subjects with confirmation of a hypodiploid karyotype (chromosome number fewer than 45) ** Cohort B: Subjects with cytogenetic confirmation of the chromosomal translocation t(17;19) (Cohort B) *. Cohort C: Infants w/ newly diagnosed KMT2A rearranged B-ALL classified as very high risk by the following criteria: ** Age < 3 months at diagnosis ** Age < 6 months and white blood cell count (WBC) > 300,000 x 10^9/L at diagnosis or a poor prednisone response in induction ** Minimal residual disease (MRD) positive > 0.01 (or polymerase chain reaction [PCR] > 10^4) after 2 courses of standard infant acute lymphoblastic leukemia (ALL) therapy * Cohort D: Subjects in a first or greater central nervous system (CNS) relapse, prior to therapy with cranial radiation (XRT) or hematopoietic stem cell transplant (HSCT) for the current relapse
• Expression of CD19 on leukemic blasts demonstrated by flow cytometry of bone marrow, cerebrospinal fluid, or peripheral blood
• A 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) =< 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 ALL infiltration of the liver
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea and < grade 3 hypoxia; diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the physician-investigator
• Left ventricular shortening fraction (LVSF) >= 28%, or left ventricular ejection fraction (LVEF) >= 45% by echocardiogram. In cases where qualitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the echocardiogram (ECHO) shows qualitatively normal ventricular function will suffice
• Adequate performance status defined as Lansky or Karnofsky score >= 50
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• For subjects with a CNS relapse, prior cranial XRT or bone marrow transplantation (BMT) for the current relapse is an exclusion
• Active hepatitis B or active hepatitis C
• Human immunodeficiency virus (HIV) 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
• CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
• Pregnant or nursing (lactating) women
• Uncontrolled active infection