CD19 Chimeric Antigen Receptor (CAR) T Cells in Adults With Relapsed/Refractory CD19 Positive Acute Lymphoblastic Leukemia

Exclusion Criteria

• •1. Clinically Active central nervous system (CNS) involvement by malignancy
• •2. History or presence of uncontrolled underlying seizure disorder not related to B-ALL
• •3. History of or active clinically significant cardiovascular dysfunction, including any of the following:
• •* History of stroke within 24 months prior to the CD19 CAR T cells infusion or with ongoing sequelae
• •* History of transient ischemic attack within 12 months prior to the CD19 CAR T cells infusion
• •* History of myocardial infarction within 36 months prior to the CD19 CAR T cells infusion
• •* Symptomatic congestive heart failure (NYHA class III/IV), unstable angina pectoris, cardiac arrhythmia requiring therapy
• •* Uncontrolled arrhythmias, or history of or active ventricular arrhythmia requiring medication
• •* Active or history of coronary heart disease that remains symptomatic
• •* Active or history of unstable or stable angina
• •* Left ventricular ejection fraction (LVEF) \< 45% confirmed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) scan
• •4. Creatinine clearance \< 60
• •5. Concomitant genetic syndromes associated with Bone Marrow (BM) failure states, such as Fanconi anemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome; patients with Down syndrome are not excluded
• •6. Burkitt lymphoma/leukemia
• •7. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
• •8. Treatment with any prior gene therapy product (except prior CAR-T cell therapy)
• •9. Positive HIV test within 8 weeks of screening
• •10. Serologic status reflecting active hepatitis B or C infection: Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
• •11. Received an investigational medicinal product on trial within the 30 days prior to screening
• •12. Pregnant
• •13. Lactating
• •14. Women of child-bearing potential and all male participants, unless using highly effective methods of contraception for 1 year after CAR-T infusion
• •15. Therapeutic systemic doses of steroids (\>=0.5mg/kg prednisone equivalent) must be stopped \>72 hours prior to lymphodepletion
• •16. TKIs and hydroxyurea must be stopped \>72 hours prior to lymphodepletion
• •17. The following drugs must be stopped \>1 week prior to lymphodepleting chemotherapy:
• •vincristine, 6- mercaptopurine, 6-thioguanine, methotrexate 2 weeks prior to CART infusion: salvage chemotherapy (e.g., clofarabine, cytosine arabinoside \>100 mg/m2
• •, anthracyclines, cyclophosphamide, methotrexate ≥25 mg/m2
• •), excluding the required lymphodepleting chemotherapy drugs
• •18. Pegylated asparaginase must be stopped \>4 weeks prior to CAR T cell infusion
• •19. CNS disease prophylaxis and/or intrathecal chemotherapy must be stopped \>1 week prior to CAR T cell infusion
• •20. Radiation therapy at non-CNS site must be completed \>2 weeks prior to CAR T Cell infusion
• •21. CNS-directed radiation must be completed \>8 weeks prior to CAR T cell infusion
• •22. Known History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study (including, but not limited to, cyclophosphamide and fludarabine used in the lymphodepleting chemotherapy, DMSO used as a cryoprotectant in the cell media, etc.)
• •23. Autologous transplant within 6 weeks of planned CAR-T cell infusion
• •24. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy.
• •25. Primary Immunodeficiency Patients:
• •• Patients with known primary immunodeficiency disorders are excluded due to increased risk of adverse outcomes.
• •26. Recent Live Vaccine Administration:
• •* Patients who have received a live vaccine within 4 weeks prior to enrolment are excluded.
• •* Additionally, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy