CART22-65s and huCART19 CAR T Cells for the Treatment of Relapsed or Refractory B-ALL

Inclusion Criteria

• Signed informed consent form must be obtained prior to any study procedure. Labs, marrows, or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required window
• Patients with documented CD19+ and/or CD22+ ALL/LLy: * Cohort A: Patients with relapsed or refractory ALL/LLy who have not previously received CAR T-cell therapy: ** 2nd or greater relapse (marrow or extramedullary) OR ** Any relapse after allogeneic hematopoietic cell transplantation (HSCT) and ≥ 4 months from HSCT at enrollment OR ** Refractory disease defined as having not achieved an MRD-negative (by multiparameter flow cytometry) and CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy, or 1 cycle of reinduction therapy for patients in first relapse OR ** Newly diagnosed National Cancer Institute (NCI) high-risk B-ALL with induction failure, defined as a M3 bone marrow (≥ 25%) blasts at the end of Induction chemotherapy OR ** First bone marrow relapse of B-ALL at < 36 months after initial diagnosis OR ** First or greater central nervous system (CNS) relapse of B-ALL ** Ineligible for allogeneic HSCT because of: *** Comorbid disease *** Other contraindications to HSCT conditioning regimen *** Lack of suitable donor *** Prior HSCT *** Declines HSCT as the therapeutic option after documented discussion, with expected outcomes, and the role of HSCT with a bone marrow transplantation (BMT) physician not part of the study team. * Cohort B: Patients with poor response to prior B cell directed engineered cell therapy ** Partial response or no response to prior cell therapy ** CD19+ and/or CD22+ relapse after prior cell therapy, defined as bone marrow blasts >0.01% by multiparameter flow cytometry or evidence of extramedullary disease. ** Demonstrated early ( ≤ 6 months from infusion) B cell recovery suggesting loss of engineered cells
• Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy
• Documentation of CD19 and/or CD22 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue by flow cytometry at the time of last detectable disease. If the patient has experienced a relapse after CD19-directed and/or CD22-directed therapy, flow cytometry should be evaluated after this therapy to demonstrate CD19 and/or CD22 expression
• Age 0-29 years
• Serum creatinine based on age/gender as follows: Maximum serum creatine (mg/dL) * 0 to < 2 years: 0.6 (male); 0.6 (female) * 2 to < 6 years: 0.8 (male); 0.8 (female) * 6 to < 10 years: 1.0 (male); 1.0 (female) * 10 to < 13 years: 1.2 (male); 1.2 (female) * 13 to < 16 years: 1.5 (male); 1.4 (female) * ≥ 16 years: 1.7 (male); 1.4 (female)
• Alanine aminotransferase (ALT) within 5x upper limit of normal (ULN) in the absence of ALL infiltration of the liver
• Bilirubin ≤ 3x 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 ALL 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 test (DLCO) ≥ 40% (corrected for anemia) if pulmonary function 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. 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 Lanksy 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
• Human immunodeficiency virus (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
• CNS 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