Safety, Tolerability, and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy for r/r B-ALL: a Clinical Trial

Официальное название

Safety, Tolerability and Pharmacokinetics of Donor-derived CD19 CAR Therapy Bridged Allogeneic Haematopoietic Stem Cell Transplantation and Sequential Donor-derived CD22 CAR Therapy in Refractory or Relapsed B Cell Acute Lymphoblastic Leukemia: a Clinical Trial

Обзор

This is an investigator-initiated, single-arm, open-label, non-randomised phase I clinical study. The objective of this trial is to evaluate the safety, tolerability and pharmacokinetics of donor-derived CD19 CAR Therapy bridged Allo-HSCT and sequential donor-derived CD22 CAR Therapy for r/r B-ALL and to explore the efficacy of this therapy preliminarily. The primary endpoints are incidence and type of dose-limiting toxicity (DLT) within 28 days (i.e., 43 days after donor-derived CD19 CAR T-cell infusion) after donor-derived CD19 CAR T-cell therapy bridged allogeneic haematopoietic stem cell transplantation; total number, incidence and severity of adverse events from donor-derived CD19 CAR T cell infusion back to 30 days after donor-derived CD22 CAR T cell infusion (i.e., within 120 days of donor-derived CD19 CAR T cell infusion). The secondary endpoints are total number, incidence and severity of adverse events from 120 days to 2 years after donor-derived CD19 CAR T-cell infusion; ORR(CR+CRi) on days 45, 90, 120; duration of response(DOR), event-free survival(EFS), overall survival(OS); pharmacokinetics characteristics. The trial plan to enroll 3\~12 cases in dose escalation phase and 36 cases in dose expansion phase.

Вмешательства

• Препарат Donor-derived CD19 CAR Therapy Bridged Allo-HSCT and Sequential Donor-derived CD22 CAR Therapy
  Peripheral blood mononuclear cells for the production of CD19 CAR T cells and CD22 CAR T cells are collected from donors and haematopoietic stem cells are collected from donors.

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Within 43 days of donor-derived CD19 CAR T-cell infusion]
• Adverse events (AEs) [Срок оценки: Within 120 days of donor-derived CD19 CAR T-cell infusion]

Вторичные конечные точки (8)

• Long-term Adverse events (AEs) [Срок оценки: From 120 days to 2 years after donor-derived CD19 CAR T-cell infusion]
• Objective response rate(ORR) [Срок оценки: day 30, day 45, day 90]
• Duration of response (DOR) [Срок оценки: Up to 2 years]
• Event-free survival (EFS) [Срок оценки: Up to 2 years]
• Overall survival (OS) [Срок оценки: Up to 2 years]
• The persistence of CD19/CD22 CAR T cells. [Срок оценки: Up to 2 years]
• The Maximum concentration (Cmax) of CD19/CD22 CAR T cells. [Срок оценки: Up to 2 years]
• The time to maximum plasma concentration (Tmax) of CD19/CD22 CAR T cells. [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

\- Patients will be enrolled only if they meet all the inclusion criteria.

• Patients with relapsed or refractory CD19+/CD22+ (FCM >95%) B-cell acute lymphoblastic leukaemia who have progressed despite or are intolerant to all standard therapies, including, but not limited to, immunotherapies such as Blinatumomab (BITE), Tyrosine kinase inhibitors (TKI), CAR T-cell therapy, etc.; Currently available therapies have a limited prognosis and there are no available curative treatment options (e.g., HSCT or chemotherapy);
• Peripheral blood tumour burden ≥60% or severe peripheral blood cytopenia, unsuitable/unable to collect autologous lymphocytes;
• 1 to 18 years old;
• Patient's expected survival time ≥ 60 days;
• Physical status: ECOG score 0-2;
• Availability of allogeneic donors (HLA-identical or HLA-haploidentical) DSA-negative for collection of peripheral blood mononuclear cells and peripheral blood stem cells;
• Sign an informed consent form during the screening period. Pediatric patients under 8\~18 years of age need to have sufficient awareness to voluntarily sign an informed consent form, and their legal representatives (guardians) also need to voluntarily sign an informed consent form; pediatric patients aged 1\~7 years can only be recruited after their legal guardians have voluntarily signed an informed consent form.

Критерии исключения

• Patients who meet any of the following criteria are not eligible for enrolment.

• Patients who have received previous haematopoietic stem cell transplantation (including peripheral blood haematopoietic stem cell transplantation and bone marrow haematopoietic stem cell transplantation);
• Intracranial hypertension or cerebral impaired consciousness;
• Symptomatic heart failure or severe cardiac arrhythmia;
• Symptoms of severe respiratory failure;
• With other types of malignant tumours;
• Diffuse intravascular coagulation;
• Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
• Suffering from sepsis or other uncontrollable infections;
• Suffering from uncontrollable diabetes mellitus;
• Severe mental disorders;
• Have significant intracranial lesions on cranial MRI (excluding intracranial masses caused by central nervous system leukaemia);
• Have organ transplant history;
• Female patients (patients of childbearing potential) with positive blood HCG test;
• Hepatitis (including Hepatitis B and Hepatitis C) and positive screening for AIDS and syphilis;
• No allogeneic donor suitable for collection of peripheral blood lymphocytes and haematopoietic stem cells.

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 · 1 центр

• Beijing GoBroad Hospital — Пекин

Идентификаторы

NCT: NCT06326008 · BJGBYY-IIT-LCYJ-2023-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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