A Study of CNCT19 Treatment in Children and Adolescent r/r ALL Patients(Pediatric)

Официальное название

A Phase Ib/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of CNCT19 in Children and Adolescent(Pediatric) Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

Обзор

This is a multi-center, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 treatment in Children and Adolescent (pediatric) patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).

Подробное описание

This trial is a multi-center, open label, single-arm, phase Ib/II trial to evaluate the safety and efficacy of CNCT19 in Children and Adolescent(aged 3\~18 years old) patients (pediatric) with r/r B-cell ALL.

The phase Ib part of the trial is to evaluate the safety, optimal dose of CNCT19, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Children and Adolescent patients with r/r B-cell ALL.

The phase II part of the trial is to evaluate the efficacy and safety of CNCT19 in in the treatment of Children and Adolescent patients with r/r B-cell ALL.

The study includes screening, pre-treatment (Cell Product manufacture \& lymphodepletion), CNCT19 infusion , safety and efficacy follow-up, and survival follow-up. All subjects who have received CNCT19 infusion will be followed for up to 2 years.

Вмешательства

• Биопрепарат single dose of CNCT19
  Autologous 2nd generation CD19-directed CAR-T cells, single infusion intravenously. Lymphodepletion treatment: Drugs:Fludarabine Drugs: Cyclophosphamide

Первичные конечные точки

• Overall Remission Rate (ORR) [Срок оценки: within 3 months]

Вторичные конечные точки (12)

• Overall complete Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators [Срок оценки: within 3 months]
• Overall Remission Rate (ORR) as determined by IRC and Investigators [Срок оценки: at the end of month 3]
• Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators [Срок оценки: at the end of Month 3]
• Best overall response (BOR) [Срок оценки: up to 2 years]
• Duration of remission (DOR) [Срок оценки: to data cutoff date]
• Allogeneic Stem Cell Transplant (Allo-SCT) rate [Срок оценки: First infusion date of CNCT19 to data cutoff date(up to 2 years)]
• Relapse Free Survival (RFS) [Срок оценки: 2 years]
• Overall survival (OS) [Срок оценки: 2 years]
• Treatment-Emergent Adverse Events [Срок оценки: up to 2 years]
• Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities [Срок оценки: From CNCT19 infusion to date of data cutoff (maximum: 2 years)]
• In vivo cellular Pharmacokinetic (PK) profile of CNCT19 [Срок оценки: Up to 3 months(BM sample); Up to 2 years(Blood sample)]
• Pharmacokinetic (PK)- Cmax of CNCT19 [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian)
• Age 3 to 18. Weight ≥10kg
• Relapsed or refractory acute lymphoblastic leukemia (ALL).
• Documentation of CD19 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening.
• Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.
• Karnofsky (age ≥ 16 years) performance status ≥ 70 or Lansky (age < 16 years) performance status ≥ 50 at screening
• Organ function requirements: All patients must have adequate renal and liver functions

Критерии исключения

• Active Central Nervous System (CNS) involvement by malignancy.
• Isolated extra-medullary disease relapse.
• Patients with Burkitt's lymphoma/leukemia, mixed phenotypic acute leukemia and Chronic Myelogenous Leukemia in Blast Crisis
• History of concomitant genetic syndrome
• Patients with acute graft-versus-host disease (GVHD) or moderate-to-severe chronic GVHD within 4 weeks before screening.
• Active systemic autoimmune disease
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive).
• Patients with active infections at screening.
• Patients who received specified chemotherapy before CNCT19 infusion
• Radiotherapy before CNCT19 infusion:

Non-CNS site of radiation completed < 4 weeks prior to CNCT19 Infusion; CNS directed radiation completed < 8 weeks prior to CNCT19 infusion.

• Donor lymphocyte infusion (DLI) must be stopped > 6 week prior to CNCT19 infusion.
• Has had treatment with any prior CAR-T therapy.
• Life expectancy < 3 months.

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

Китай · 9 центров

• The Second Hospital of Anhui Medical University — Хэфэй
• Children's Hospital of Chongqing Medical University — Чунцин
• Guangzhou Women and Children's Medical Center — Гуанчжоу
• Nanfang Hospital — Гуанчжоу
• Union Hospital Tongji Medical College Huazhong University of Science of Technology — Ухань
• Children's Hospital of Nanjing Medical University — Нанкин
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou
• The First Affilicated Hospital of Nanchang University — Nanchang
• … и ещё 1 центр

Идентификаторы

NCT: NCT05667506 · HY001103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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