CAR T-cell therapy for relapsed or refractory T-cell leukemia

Anti-CD7 Protein Expression Blocker (PEBL) Chimeric-Antigen Receptor (CAR) T-Cell Therapy for Relapsed/ Refractory T-Lineage Acute Lymphoblastic Leukaemia (CARTALL)

This study is testing a new CAR T-cell therapy for patients with hard-to-treat T-cell leukemia to see if it can help them achieve longer-lasting remissions while protecting normal cells.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 6 Months to 65 Years
• Sex: All
• Sponsor: National University Hospital, Singapore (other)
• Drugs / interventions: CAR-T, chemotherapy, CAR T, CART
• Locations: 1 site (Singapore)
• Trial ID: NCT05043571 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of anti-CD7 CAR T-cells in patients suffering from relapsed or refractory T-lineage acute lymphoblastic leukemia (T-ALL). The approach involves targeting CD7, a marker present in T-ALL cells, while minimizing damage to normal T-cells through the use of an anti-CD7 Protein Expression Blocker (PEBL). Patients will receive CAR T-cell therapy designed to induce deeper and more durable remissions by effectively targeting the leukemia cell population. The study aims to address the challenges faced in treating T-cell malignancies with existing CAR T-cell therapies.

Who should consider this trial

Good fit: Ideal candidates include individuals with relapsed or refractory T-cell acute lymphoblastic leukemia who meet specific diagnostic and treatment failure criteria.

Not a fit: Patients with non-T-cell malignancies or those who do not meet the eligibility criteria for relapsed or refractory T-ALL may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat T-cell leukemia, potentially leading to improved remission rates.

How similar studies have performed: Other studies have shown promise with CAR T-cell therapies targeting different markers, but this specific approach targeting CD7 in T-ALL is relatively novel.

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.

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)

Where this trial is running

Singapore

• Allen Yeoh Eng Juh — Singapore, Singapore (RECRUITING)

Study contacts

• Principal investigator: Allen Yeoh, M.D — National University Hospital, Singapore
• Study coordinator: Allen Yeoh, M.D

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