CARTALL: Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia

NCT ID: NCT05043571

Last Updated: 2021-09-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-08
• Study Completion Date: 2026-11-01

Brief Summary

The objective of this study is to assess the safety and efficacy of anti-CD7 CAR T-cells in patients with refractory or relapsed T-lineage acute lymphoblastic leukemia (T-ALL).

Detailed Description

A major obstacle to the development of effective CAR T-cells for T-cell malignancies is that the surface marker profile of malignant T-cells largely overlaps that of activated T lymphocytes. We developed a CAR T-cell approach that targets CD7, a T-cell marker highly expressed in all cases of T-cell ALL, including ETP-ALL. Its expression is also highly stable even in T-ALL cells exposed to chemotherapy. To prevent fratricide effect of the T cells, surface CD7 expression are effectively downregulated with the expression of an anti-CD7 Protein Expression Blocker (PEBL). Patients will receive anti-CD7 PEBL CART-cells. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions.

Conditions

Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia; Lymphoblastic Leukemia, Acute Adult; Lymphoblastic Leukemia in Children; CAR; CAR T-Cell-Related Encephalopathy Syndrome; Refractory Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

Single arm Phase I Clinical Trial

Group Type: EXPERIMENTAL

CAR T-cell therapy

Intervention Type: BIOLOGICAL

This is a single-centre, phase I study to determine the efficacy and safety of CAR T-cell therapy in patients with high-risk T-ALL, refractory or relapsed T-ALL.

Interventions

CAR T-cell therapy

This is a single-centre, phase I study to determine the efficacy and safety of CAR T-cell therapy in patients with high-risk T-ALL, refractory or relapsed T-ALL.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Diagnosis/ Disease define as:

1. Relapsed T-cell acute lymphoblastic leukaemia/ lymphoma as defined by:

Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry

Or CNS disease as defined as > 5 WBCs/ uL in CSF with morphological evidence of blasts or biopsy proven recurrence in the eye or brain

Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites

2. Induction failure as defined by:

MRD = or > 1% by flow cytometry at the end of induction on day 33

Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy

3. Refractory disease as defined by:

MRD = or > 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy

• Minimum level of pulmonary reserve defined as Grade ≤ 1 dyspnoea and oxygen saturation (SpO2) of > 95% on room air
• Left ventricular systolic function (LVSF) ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction (LVEF) ≥ 45% confirmed by echocardiogram within 3 months of screening
• Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening
• Normal Age-adjusted eGFR Creatinine Clearance within 3 months of screening
• Alanine aminotransferase ≤ 5 times the upper limit of normal for age
• Patients with > 99% CD7 expression on blast cells will be eligible for anti-CD7 PEBL-CAR-T cell infusion.

• Patients who test positive on urine pregnancy testing and are pregnant or are lactating
• Concomitant genetic syndromes associated with bone marrow failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other bone marrow failure syndrome with the exception of Down syndrome
• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
• Active or latent hepatitis B or hepatitis C infections within 8 weeks of screening, or any uncontrolled infection at screening
• Positive Human Immunodeficiency Virus (HIV) test within 8 weeks of screening
• Grade 2 to 4 acute graft-vs-host disease (GVHD) or extensive chronic GVHD
• Received an investigational medicinal product within 30 days of screening
• Central nervous system : Uncontrolled seizures or status epilepticus; increased intra-cranial pressure as evidenced by papilledema and CSF opening pressure > 20 cm water; decreased conscious state (any cause)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Allen Yeoh, M.D

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Dario Campana, M.D, PhD

Role: STUDY_DIRECTOR

National University of Singapore

Locations

Allen Yeoh Eng Juh

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Allen Yeoh, M.D

Role: CONTACT

paeyej@nus.edu.sg

+65 6772 2002

Facility Contacts

Allen Yeoh, M.D

Role: primary

paeyej@nus.edu.sg

+(65) 6772 2002

Zhiwei Chen, BSc.

Role: backup

chen.zhiwei@nus.edu.sg

+(65) 6772 4406

Other Identifiers

2020/01325

Identifier Type: -

Identifier Source: org_study_id