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

March 7, 2023 updated by: KK Women's and Children's Hospital
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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:

  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

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Singapore
      • Singapore, Singapore, 229899
        • Recruiting
        • KK Women's and Children's Hospital
        • Contact:
        • Principal Investigator:
          • Shui Yen Soh
      • Singapore, Singapore, 169608
        • Recruiting
        • Singapore General Hospital
        • Contact:
          • Aloysius Ho, MD
        • Principal Investigator:
          • Aloysius Ho

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 second to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Protocol Feasibility
Time Frame: 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.
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: 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.
6 months
Toxicity Evaluations
Time Frame: 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.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

KK Women's and Children's Hospital

Collaborators

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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2022

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2026

Study Registration Dates

First Submitted

August 1, 2022

First Submitted That Met QC Criteria

December 4, 2022

First Posted (Actual)

December 13, 2022

Study Record Updates

Last Update Posted (Estimate)

March 9, 2023

Last Update Submitted That Met QC Criteria

March 7, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHCELL18P1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoblastic Leukemia

Clinical Trials on Anti-CD19 CAR T-cells

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe