Human AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Lymphoid Malignancies

Inclusion Criteria:

• Must have relapsed or refractory non-Hodgkin lymphoma (NHL) (Group A - NHL/CLL),chronic lymphocytic leukemia (Group A - NHL/CLL) or acute lymphoblastic leukemia (Group B - ALL) treated with at least two lines of therapy. Disease must have eitherprogressed after the last regimen or presented failure to achieve complete remissionwith the last regimen.

• The participant's malignancy is CD19 positive, either by immunohistochemistry orflow cytometry analysis on the last biopsy available or peripheral blood forcirculating disease.

• Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2

• Total bilirubin ≤ 1.5 times the institutional upper limit of normal unless bilirubinrise is due to Gilbert's syndrome (maximum 2 time normal) or of non-hepatic origin

• AST (SGOT) ≤ 3 times institutional upper limit of normal

• ALT (SGPT) ≤ 3 times institutional upper limit of normal

• Serum Creatinine ≤ 2 times the institutional upper limit of normal and creatinineclearance ≥ 30 mL/min (calculated or measured)

• Must have adequate pulmonary function as defined as pulse oximetry ≥ 92% on roomair.

• Must have adequate cardiac function as defined as left ventricular ejectionfraction≥ 40% in the most recent echocardiogram.

• Absolute Lymphocyte Count >100/microliter (uL)

• Participants (or legal guardians) must have the ability to understand and thewillingness to sign a written informed consent document.

• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use a contraceptive method with a failure rate of < 1%per year during the treatment period and for at least 90 days after the humananti-CD19 CAR-T cell infusion. A woman is considered to be of childbearing potentialif she is postmenarcheal, has not reached a postmenopausal state (< 12 continuousmonths of amenorrhea with no identified cause other than menopause), and has notundergone surgical sterilization (removal of ovaries and/or uterus). Examples ofcontraceptive methods with a failure rate of < 1% per year include bilateral tuballigation, male sterilization, hormonal contraceptives that inhibit ovulation,hormone-releasing intrauterine devices, and copper intrauterine devices. Thereliability of sexual abstinence should be evaluated in relation to the duration ofthe clinical trial and the preferred and usual lifestyle of the patient. Periodicabstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andwithdrawal are not acceptable methods of contraception.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) oruse contraceptive measures, and agreement to refrain from donating sperm, as definedbelow: With female partners of childbearing potential, men must remain abstinent oruse a condom plus an additional contraceptive method that together result in afailure rate of < 1% per year during the treatment period and for at least 6 monthsafter the human anti-CD19 CAR-T cell infusion. Men must refrain from donating spermduring this same period. With pregnant female partners, men must remain abstinent oruse a condom during the treatment period and for at least 6 months after the humanantiCD19 CAR-T cell infusion to avoid potential embryonal or fetal exposure. Thereliability of sexual abstinence should be evaluated in relation to the duration ofthe clinical trial and the preferred and usual lifestyle of the patient. Periodicabstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) andwithdrawal are not acceptable methods

Exclusion Criteria:

• Autologous transplant within 6 weeks of planned CAR-T cell infusion.

• Allogeneic stem cell transplant within 3 months of planned CAR-T cell infusion andpatients must be off immunosuppressive agents.

• Active graft versus host disease.

• Active central nervous system or meningeal involvement by lymphoma or leukemia.Subjects with untreated brain metastases/central nervous system (CNS) disease willbe excluded from this clinical trial because of their poor prognosis and becausethey often develop progressive neurologic dysfunction that would confound theevaluation of neurologic and other adverse events.

• Participants with a history of CNS or meningeal involvement must be in a documentedremission by cerebrospinal fluid (CSF) evaluation and contrast-enhanced MRI imagingfor at least 90 days prior to registration.

• Second active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast).

• A minimum of 28 days must have elapsed between prior treatment with investigationalagent(s) and the day of lymphocyte collection.

• HIV seropositivity.

• Participants with uncontrolled intercurrent illness including, but not limited toongoing or active infection, symptomatic congestive heart failure, unstable anginapectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/socialsituations that would limit compliance with study requirements.

• Pregnant or breastfeeding women are excluded from this study because CAR-T celltherapy may be associated with the potential for teratogenic or abortifacienteffects. Women of childbearing potential must have a negative serum pregnancy test.Because there is an unknown, but potential risk for adverse events in nursinginfants secondary to treatment of the mother with CAR-T cells, breastfeeding shouldbe discontinued. These potential risks may also apply to other agents used in thisstudy.

• Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasiaon screening bone marrow biopsy prior

• Serologic status reflecting active hepatitis B or C infection. Patients that arepositive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), orhepatitis C antibody must have a negative polymerase chain reaction (PCR) prior toenrollment. (PCR positive patients will be excluded.)

• Participants with history of clinically relevant CNS pathology such as epilepsy,seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severebrain injuries, dementia and Parkinson's disease.

• History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupuserythematosus) with requirement of immunosuppressive medication within 6 months.