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

Phase 2RecruitingNCT05648019

KK Women's and Children's Hospital40 enrolled

Overview

The purpose of this study is to describe feasibility of delivering point-of-care manufactured CD19-directed CAR T-cell therapy to patients with relapsed/ refractory B-lineage leukaemia/ lymphoma.

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: 1. Screening phase: Eligibility; enrolment 2. Preparatory phase: Bridging therapy (if required); leukapheresis; CAR T manufacturing; lymphodepletion. 3. Treatment phase: Infusion of single dose of anti-CD19 CAR T-cells 4. Follow-up Phase: Efficacy and safety monitoring up to 24 months

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphoblastic Leukemia Lymphoblastic Leukemia in Children Lymphoblastic Leukemia, Acute Adult

Eligibility

Sex: ALLMin age: 0 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Eligible disease conditions: 1. 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 2. 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. 2. Age at screening: 1. \< 18 years (paediatric group); or 2. ≥ 18 years (adult group) 3. Adequate organ functions: 4. Life expectancy more than 12 weeks. 5. Karnofsky (age ≥ 16 years) or Lansky (age \< 16 years) performance status ≥ 50 at screening. 6. 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

Outcomes

Primary Outcomes

Protocol Feasibility

To describe feasibility of delivering point-of-care manufactured CD19-directed CAR T-cell therapy to patients with relapsed / refractory B-lineage leukaemia / lymphoma by assessing number and percentage of enrolled patients who have successful manufacturing of CAR T-cell product, and number and percentage of enrolled patients who go on to receive the CAR T-cell product.

Time frame: 3 years

Secondary Outcomes

Overall Response Rate

To evaluate percentage of patients with complete response or partial response at 28 days, 3 months and 6 months post-infusion of the CD19-directed CAR T-cells.

Time frame: 6 months

Toxicity Evaluations

To evaluate overall incidence (percentage of infused patients) of toxicities post-infusion of CAR T-cells, in particular cytokine release syndrome (CRS) and neurotoxicity, and percentage with Grade 3 and above CRS and neurotoxicity following ASTCT definition and severity grading, and other toxicities as assessed by CTCAE v5.0.