CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory B-Lineage Leukaemia / Lymphoma - A Feasibility Protocol

Inclusion Criteria:

1. Eligible disease conditions:
2. Relapsed or refractory B-cell ALL (all must be satisfied)

• Presence of lymphoblasts in bone marrow aspirate by morphologic assessmentor positive minimal residual disease at screening.
• Relapsed or refractory or ineligible for HSCT
• For relapsed B-ALL: Documentation of CD19 tumour expression (e.g. by flowcytometry) demonstrated in bone marrow or peripheral blood within 3 monthsof study entry

2. Relapsed or refractory large B-cell lymphoma after two or more lines of systemictherapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified,primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCLarising from follicular lymphoma.
3. Age at screening:
4. < 18 years (paediatric group); or
5. ≥ 18 years (adult group)
6. Adequate organ functions:
7. Life expectancy more than 12 weeks.
8. Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 atscreening.
9. Must meet the institutional criteria to undergo leukapheresis or have a leukapheresisproduct of non-mobilized cells received and accepted by the manufacturing site.

Exclusion Criteria: Patients with any of the following will be excluded:

• B-ALL with isolated extramedullary disease relapse
• Patients with concomitant genetic syndrome: such as patients with Fanconi anaemia,Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.Patients with Down syndrome will not be excluded.
• Patients with Burkitt's lymphoma/leukaemia (i.e. patients with mature B-cell ALL;leukaemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL,with FAB L3 morphology and /or a MYC translocation)
• Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),or any uncontrolled infection at screening
• Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
• Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
• Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines. Subjectswith CNS-2 involvement or with history of CNS disease that have been actively treatedare eligible.
• Patient has an investigational medicinal product within the last 30 days prior toscreening.
• Pregnant or nursing women.
• Women of childbearing potential (defined as all women physiologically capable ofbecoming pregnant) and all male participants, unless they are using highly effectivemethods of contraception for a period of 1 year after the CAR T-cell infusion. Allfemale patients of childbearing potential must have a negative pregnancy testperformed within 48 hours before infusion of CAR T-cells. The following are not strictly exclusion criteria but must be discussed with PI/Site-PI:
• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curativeintent and with no evidence of active disease
• Treatment with any prior gene therapy product
• Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19therapy