Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients

Inclusion Criteria:

* Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes; Burkitt lymphoma/ Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
* Patients \<25 years of age and weighing at least 6 kg at the time of screening
* Patients who have relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant) or are primary refractory (have not achieved a CR or PR after the first line of therapy)
* Measurable disease by radiological criteria in all patients at the time of screening. Patients with Burkitt leukemia who don't meet radiological criteria must have bone marrow involvement of \>25% by local assessment of bone marrow aspirate and/or biopsy.
* Karnofsky (age ≥16 years) or Lansky (age \<16 years) performance status ≥60.
* Adequate bone marrow reserve without transfusions (transfusion \>2 weeks prior to laboratory assessment is allowed) defined as:

  1. Absolute neutrophil count (ANC) \>1000/mm3
  2. Platelets ≥50000//mm3
  3. Hemoglobin ≥8.0 g/dl
* Adequate organ function defined as:

  1. a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine (mg/dL) Age Male Female

     1 to \<2 years 0.6 0.6 2 to \<6 years 0.8 0.8 6 to \<10 years 1.0 1.0 10 to \<13 years 1.2 1.2 13 to \<16 years 1.5 1.4

     ≥16 years 1.7 1.4
  2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN) for age
  3. Total bilirubin \<2 mg/dL (for Gilbert's Syndrome patients total bilirubin \<4 mg/dL)
  4. Adequate pulmonary function

  i. Oxygen saturation of \>91% on room air ii. No or mild dyspnea (≤Grade 1)
* Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.

Exclusion Criteria:

* Prior gene therapy or engineered T cell therapy.
* Prior treatment with any anti-CD19 therapy.
* Allogeneic hematopoietic stem cell transplant (HSCT) \<3 months prior to screening and ≤4 months prior to infusion.
* Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) in patients who received prior allogeneic HSCT.
* Prior diagnosis of malignancy other than study indication, and not disease free for 5 years.
* Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
* Presence of active hepatitis B or C as indicated by serology.
* Human Immunodeficiency Virus (HIV) positive test.
* Active neurological autoimmune or inflammatory disorders not related to B cell NHL (eg: Guillain-Barre syndrome, Amyotrophic Lateral Sclerosis)
* Active central nervous system (CNS) involvement by malignancy.
* Patients with B-cell NHL in the context of post-transplant lymphoproliferative disorders (PTLD) associated lymphomas.