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

National University Health System (NUHS)

Status and phase

Enrolling

Phase 1

Conditions

Lymphoblastic Leukemia in Children

CAR

Lymphoblastic Leukemia

Lymphoblastic Leukemia, Acute Adult

Lymphoblastic Leukemia, Acute, Childhood

Refractory Leukemia

CAR T-Cell-Related Encephalopathy Syndrome

Treatments

Biological: CAR T-cell therapy

Study type

Interventional

Funder types

Other

Identifiers

NCT05043571

2020/01325

Details and patient eligibility

About

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).

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

6 months to 65 years old

Volunteers

No Healthy Volunteers

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)