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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Биопрепарат 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.

Первичные конечные точки

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

Вторичные конечные точки (2)

• 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. [Срок оценки: 30 days]
• 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 [Срок оценки: 1 month to 5 years]

Критерии участия

Критерии включения

• Diagnosis/ Disease define as:

• 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

• 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

• 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.

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Сингапур · 1 центр

• Allen Yeoh Eng Juh — Singapore

Идентификаторы

NCT: NCT05043571 · 2020/01325

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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