CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory B-Lineage Leukaemia / Lymphoma - A Feasibility Protocol
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
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:
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Screening phase: Eligibility; enrolment
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Preparatory phase: Bridging therapy (if required); leukapheresis; CAR T manufacturing; lymphodepletion.
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Treatment phase: Infusion of single dose of anti-CD19 CAR T-cells
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Follow-up Phase: Efficacy and safety monitoring up to 24 months
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Single Arm CD19-directed CAR T-cell therapy for relapsed/refractory B-lineage leukaemia/lymphoma. |
Biological: Anti-CD19 CAR T-cells
A target per-protocol dose of vi able CD19 CAR transduced T-cells will consist of a single infusion of 0.2 to 5.0 x 10e6 lentiviral-transduced viable 41BB-CD19 CAR T-cells per kg body weight.
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Outcome Measures
Primary Outcome Measures
- Protocol Feasibility [3 years]
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.
Secondary Outcome Measures
- Overall Response Rate [6 months]
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.
- Toxicity Evaluations [6 months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eligible disease conditions:
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Relapsed or refractory B-cell ALL (all must be satisfied)
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Presence of lymphoblasts in bone marrow aspirate by morphologic assessment or positive minimal residual disease at screening.
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Relapsed or refractory or ineligible for HSCT
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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
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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.
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Age at screening:
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< 18 years (paediatric group); or
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≥ 18 years (adult group)
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Adequate organ functions:
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Life expectancy more than 12 weeks.
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Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening.
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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:
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B-ALL with isolated extramedullary disease relapse
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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.
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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)
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Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening
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Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening
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Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
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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.
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Patient has an investigational medicinal product within the last 30 days prior to screening.
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Pregnant or nursing women.
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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:
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Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
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Treatment with any prior gene therapy product
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Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Singapore General Hospital | Singapore | Singapore | 169608 | |
2 | KK Women's and Children's Hospital | Singapore | Singapore | 229899 |
Sponsors and Collaborators
- KK Women's and Children's Hospital
- Singapore General Hospital
Investigators
- Principal Investigator: Shui Yen Soh, MD, KK Women's and Children's Hospital
- Principal Investigator: Aloysius Ho, MD, Singapore General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHCELL18P1