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

Sponsor
National University Hospital, Singapore (Other)
Overall Status
Recruiting
CT.gov ID
NCT05043571
Collaborator
(none)
20
1
1
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Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Anti-CD7 Protein Expression Blocker (PEBL) Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia (CARTALL)
Anticipated Study Start Date :
Sep 8, 2021
Anticipated Primary Completion Date :
Nov 1, 2026
Anticipated Study Completion Date :
Nov 1, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Single arm

Single arm Phase I Clinical Trial

Biological: 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.

Outcome Measures

Primary Outcome Measures

  1. Proportion of participant who are flow cytometry minimal residual disease (MRD) negativity at 1 month after Anti-CD7 PEBL CAR T-cell infusion. [30 days]

    MRD levels will be determined by flow cytometry. The target sensitivity of flow MRD is <0.01% when available.

Secondary Outcome Measures

  1. Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after Anti-CD7 PEBL CAR T-cell infusion. [30 days]

    MRD levels will be determined by molecular based MRD by Ig/TCR. PCR and oncogene fusion transcript (OFT).

  2. Proportion of patient who shows CAR T-cell persistence by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion [1 month to 5 years]

    Flow cytometry will be performed on bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. 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

  1. 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.

Exclusion Criteria:
  • Failure to meet any of the inclusion criteria

  • 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)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Allen Yeoh Eng Juh Singapore Singapore 119228

Sponsors and Collaborators

  • National University Hospital, Singapore

Investigators

  • Principal Investigator: Allen Yeoh, M.D, National University Hospital, Singapore
  • Study Director: Dario Campana, M.D, PhD, National University, Singapore

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
National University Hospital, Singapore
ClinicalTrials.gov Identifier:
NCT05043571
Other Study ID Numbers:
  • 2020/01325
First Posted:
Sep 14, 2021
Last Update Posted:
Sep 14, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National University Hospital, Singapore
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 14, 2021