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

This is a single arm, open-label, multi-center, phase II feasibility study to deliver point-of-care manufactured CD19-directed CAR T-cell therapy to patients with relapsed / refractory B-lineage leukaemia / lymphoma.

The study consists of the following phases:

• Screening phase: Eligibility; enrolment
• Preparatory phase: Bridging therapy (if required); leukapheresis; CAR T manufacturing; lymphodepletion.
• Treatment phase: Infusion of single dose of anti-CD19 CAR T-cells
• Follow-up Phase: Efficacy and safety monitoring up to 24 months

Inclusion criteria

• 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.

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. Subjects with CNS-2 involvement or with history of CNS disease that have been actively treated are eligible.
• Patient has an investigational medicinal product within the last 30 days prior to screening.
• 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:

• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent 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-CD19 therapy