Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients

Exclusion Criteria

• •Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
• •Treatment with any prior gene therapy product
• •Active Central Nervous System (CNS) involvement by malignancy
• •Prior allogeneic HSCT
• •Eligible for and consenting to HSCT
• •Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
• •Investigational medicinal product within the last 30 days prior to screening
• •The following medications are excluded:
• •* Steroids: Therapeutic doses of steroids must be stopped \>72 hours prior to leukapheresis and \>72 hours prior to CTL019 infusion. However, the following physiological replacement doses of steroids are allowed: \< 12 mg/m\^2/day hydrocortisone or equivalent
• •* Immunosuppression: Any other immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis and ≥ 2 weeks prior to CTL019 infusion. This could include check point inhibitors (monoclonal antibodies and small molecule modulators)
• •* Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of leukapheresis and 2 weeks prior to infusion
• •Short acting drugs used to treat leukemia or lymphoma (e.g. tyrosine kinase inhibitors, and hydroxyurea) must be stopped \> 72 hour prior to leukapheresis and \> 72 hours prior to CTL019 infusion
• •Other cytotoxic drugs, including low dose daily or weekly maintenance chemotherapy, must not be given within 2 weeks prior to leukapheresis and within 2 weeks prior to CTL019 infusion
• •Fludarabine may be associated with prolonged lymphopenia. This should be taken into consideration when evaluating the optimal timing for leukapheresis collection.
• •* Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer
• •* CNS disease prophylaxis must be stopped \> 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
• •Prior radiation therapy within 2 weeks of infusion
• •Active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive )
• •HIV positive patients
• •Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
• •Unstable angina and/or myocardial infarction within 6 months prior to screening
• •Previous or concurrent malignancy with the following exceptions:
• •* Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
• •* In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
• •* A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
• •Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 24 hours before lymphodepletion
• •Intolerance to the excipients of the CTL019 cell product
• •Cardiac arrhythmia not controlled with medical management
• •Prior treatment with any adoptive T cell therapy
• •Patients with T-cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV positive DLBCL of the elderly, Richter's transformation, and Burkitt lymphoma
• •Patients with active neurological auto immune or inflammatory disorders (e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)