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

Primary Purpose

Lymphoblastic Leukemia, Lymphoblastic Leukemia in Children, Lymphoblastic Leukemia, Acute Adult

Status
Recruiting
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
Anti-CD19 CAR T-cells
Sponsored by
KK Women's and Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia focused on measuring CAR T-cell therapy, Relapse/Refractory, B-ALL, B-Lineage Lymphoma

Eligibility Criteria

0 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Singapore General HospitalRecruiting
  • KK Women's and Children's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

CD19-directed CAR T-cell therapy for relapsed/refractory B-lineage leukaemia/lymphoma.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 1, 2022
Last Updated
March 7, 2023
Sponsor
KK Women's and Children's Hospital
Collaborators
Singapore General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05648019
Brief Title
CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory B-Lineage Leukaemia / Lymphoma - A Feasibility Protocol
Official Title
CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy for Relapsed/Refractory B-Lineage Leukaemia / Lymphoma - A Feasibility Protocol
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
KK Women's and Children's Hospital
Collaborators
Singapore General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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: 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Lymphoblastic Leukemia in Children, Lymphoblastic Leukemia, Acute Adult, B-cell Acute Lymphoblastic Leukemia, Large B-cell Lymphoma, CAR
Keywords
CAR T-cell therapy, Relapse/Refractory, B-ALL, B-Lineage Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Arm Description
CD19-directed CAR T-cell therapy for relapsed/refractory B-lineage leukaemia/lymphoma.
Intervention Type
Biological
Intervention Name(s)
Anti-CD19 CAR T-cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Protocol Feasibility
Description
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 Outcome Measure Information:
Title
Overall Response Rate
Description
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
Title
Toxicity Evaluations
Description
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.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shui Yen Soh, MD
Phone
+65 6394 1045
Email
soh.shui.yen@singhealth.com.sg
First Name & Middle Initial & Last Name or Official Title & Degree
Germaine Liew, BS
Phone
+65 6394 5025
Email
germaine.liew.shimin@singhealth.com.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shui Yen Soh, MD
Organizational Affiliation
KK Women's and Children's Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Aloysius Ho, MD
Organizational Affiliation
Singapore General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aloysius Ho, MD
First Name & Middle Initial & Last Name & Degree
Aloysius Ho
Facility Name
KK Women's and Children's Hospital
City
Singapore
ZIP/Postal Code
229899
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shui Yen Soh
Phone
+65 6394 1045
Email
soh.shui.yen@singhealth.com.sg
First Name & Middle Initial & Last Name & Degree
Shui Yen Soh

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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