A Study of CD19 Targeted CAR T Cell Therapy in Pediatric Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL)

INCLUSION CRITERIA:

• Male or female patients < 18 years old at screening

• Patients with ≥ 6 kg body weight at screening

B ALL Cohort: r/r CD19-positive B ALL defined as:

1. Primary refractory disease defined as:

2. National Cancer Institute high risk (defined as presenting with white bloodcell count ≥ 50 × 10^9 cells/L or aged ≥ 10 years at diagnosis) patients withMRD ≥ 0.01% after first-line induction and consolidation and blinatumomab (ifallowed per country specific approvals and treatment guidelines).

3. Refractory B ALL if BM disease ≥ 25% after first line induction andconsolidation.

4. KMT2A rearranged infant ALL with MRD ≥ 1% after first line induction andblinatumomab (if allowed per country specific approvals and treatmentguidelines) or MRD ≥ 0.01% after first line induction and consolidation.

5. First relapse

6. Children's Oncology Group high risk first relapse involving BM < 36 monthsafter initial diagnosis or an isolated extramedullary relapse < 18 months afterinitial diagnosis.

7. Patients with Down syndrome and infants with KMT2A rearranged are eligible withfirst relapse at any time.

8. Refractory disease with MRD ≥ 0.01% after re-induction for first relapse (withor without blinatumomab, if allowed per country specific approvals andtreatment guidelines).

9. Second or greater relapse

10. Relapsed or refractory post-SCT: a. Relapsed or refractory disease after allogeneic transplant provided obe celinfusion occurs ≥ 3 months after SCT.

11. Philadelphia chromosome positive (Ph+) ALL:

12. Any of the above with Ph+ ALL where patient is intolerant to or has failed atleast one tyrosine kinase inhibitor (TKI) or if TKI therapy is contraindicated.

B NHL Cohort: r/r CD19-positive aggressive mature B NHL defined as 1 of the following:

1. Relapsed after one or more prior therapies (can include allogeneic and autologoushematopoietic SCT).

2. Primary refractory (have not achieved a CR or PR after the first line of therapy)with measurable, disease by radiological criteria at screening including the B NHLsubtypes: (i) diffuse large B-cell lymphoma (DLBCL), (ii) Burkitt's lymphoma, (iii)primary mediastinal large B-cell lymphoma (PMBCL) and (iv) high-grade B-celllymphoma (not otherwise specified).

• Karnofsky (age ≥ 10 years) or Lansky (age < 10 year) performance status score ≥ 50%.

• In patients with B ALL, local documentation of CD19 expression on leukemicblasts in the BM, peripheral blood, or cerebrospinal fluid (CSF) or biopsy doneno more than 30 days prior to consent. In patients treated with blinatumomab,testing should be undertaken after blinatumomab therapy has been stopped. Inpatients with mature B NHL, CD19 expression must be confirmed in a biopsy afterany CD19 targeted therapies.

• Adequate renal, hepatic, pulmonary, and cardiac function.

EXCLUSION CRITERIA:

• Diagnosis of chronic myelogenous leukemia lymphoid in blast crisis.

• History or presence of clinically relevant central nervous system (CNS) pathologyunrelated to CNS leukemia.

• Presence of CNS-3 disease or CNS-2 disease with neurological changes at screening.

• Presence of active or uncontrolled fungal, bacterial, viral, or other infectionrequiring systemic antimicrobials for management.

• Patients who had prior (< 3 months before obe-cel infusion) stem cell transplant.

• Prior CD19 targeted therapy other than blinatumomab.

• Patients who have experienced Grade ≥ 3 neurotoxicity following blinatumomab.