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

Prior treatment

• 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.
• Patient has an investigational medicinal product within the last 30 days prior to screening.
• Treatment with any prior gene therapy product
• Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy

Other illness

• B-ALL with isolated extramedullary disease relapse
• 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. Subjects with CNS-2 involvement or with history of CNS disease that have been actively treated are eligible.
• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease

Other

• Patients with any of the following will 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)
• Pregnant or nursing women.
• Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CAR T-cell infusion. All female patients of childbearing potential must have a negative pregnancy test performed within 48 hours before infusion of CAR T-cells.
  • The following are not strictly exclusion criteria but must be discussed with PI/Site-PI:

• Eligible disease conditions:
  • Relapsed or refractory B-cell ALL (all must be satisfied)
  • Presence of lymphoblasts in bone marrow aspirate by morphologic assessment or 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 flow cytometry) demonstrated in bone marrow or peripheral blood within 3 months of study entry
  • Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
• Age at screening:
  • \< 18 years (paediatric group); or
  • ≥ 18 years (adult group)
• Adequate organ functions:
• Life expectancy more than 12 weeks.
• Karnofsky (age ≥ 16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening.
• Must meet the institutional criteria to undergo leukapheresis or have a leukapheresis product of non-mobilized cells received and accepted by the manufacturing site.