A Phase 1b/2 Multi-center, De-centralized, Dose Selection Study of Autologous CD19-directed Chimeric Antigen Receptor (CAR) T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)
Autologous, unselected CD3+ lymphocytes collected from apheresis, transfected with a lentiviral vector containing a 2nd generation chimeric antigen receptor (CAR) consisting of a scFv recognizing CD19 and dual co-stimulatory intracellular signaling domains (4-1BB and CD3ζ).
• Have given written informed consent prior to any study-specific procedures; children (defined as 17 years of age or less) require guardian consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; or Karnofsky \> 50%.
• Age of 2 to 70 years at time of screening.
• A histologically or cytologically documented, CD19+ non-hodgkin's lymphoma or ALL.
• At least 1 measurable lesion or FDG-avid disease by positron-emission tomography/computed tomography (PET/CT) for lymphoma patients; quantifiable evidence of ALL in either peripheral blood or bone marrow aspirate.
• Tumor tissue (archival or recent acquisition) must be available for correlative laboratory studies (such as immunohistochemistry, and others).
• At least 2 prior systemic therapies and patient must not be eligible for potentially curative standard-of-care therapy.
• Adequate renal function (defined as Cockroft-Gault creatinine clearance \> 50 mL/min) and hepatic function (total bilirubin \< 1.5x ULN; and AST/ALT \< 3x ULN) unless directly related to malignant disease being treated for on study as demonstrated either by PET/CT imaging or by biopsy and histopathologic confirmation.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 90 days after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
⁃ Male participants should agree to not donate sperm during study period (i.e. up to 2 years following CAR T-cell administration).
⁃ Male participants with reproductive potential must agree to use medical approved contraceptives during the study and for 90 days following the last dose of study treatment.
⁃ Are reliable and willing to make themselves available for the duration of the study, and are willing to follow study procedures.