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

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05648019
• Other study ID #: SHCELL18P1
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2022
• Est. completion date: December 2026

Study information

• Verified date: March 2023
• Source: KK Women's and Children's Hospital
• Contact: Shui Yen Soh, MD
• Phone: +65 6394 1045
• Email: soh.shui.yen[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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: 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia
• CAR
• Large B-cell Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Leukemia
• Lymphoblastic Leukemia in Children
• Lymphoblastic Leukemia, Acute Adult
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Singapore	KK Women's and Children's Hospital	Singapore
Singapore	Singapore General Hospital	Singapore

Sponsors (2)

Lead Sponsor	Collaborator
KK Women's and Children's Hospital	Singapore General Hospital

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 years
Secondary	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.	6 months
Secondary	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.	6 months