Clinical Study of Universal CD19 CAR-γδ T Cell Infusion in the Treatment of Relapsed/Refractory Acute B Lymphoblastic Leukemia

Обзор

This study is an open-label, single-arm clinical trial designed to evaluate the safety and tolerability of QH103 cell infusion in subjects with CD19-positive R/R B-ALL.

Вмешательства

• Препарат Cyclophosphamide
  Eligible subjects will undergo lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises cyclophosphamide (500-1000 mg/m² administered 3 days).
• Препарат Fludarabine
  Eligible subjects will receive lymphodepletion chemotherapy 5 to 3 days prior to cell infusion. The recommended lymphodepletion regimen comprises fludarabine (30-40 mg/m² administered 3 days).
• Биопрепарат QH103 Cell Injection
  Biological: CD19 CAR-γδT cell Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with dose escalation (3+3) : dose 1 (1×10\^8 CAR+cells) ,dose 2 (3× 10\^8 CAR+cells).

Первичные конечные точки

• Adverse Event [Срок оценки: 12 months]
• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: 28 days]

Вторичные конечные точки (3)

• PK(Pharmacokinetics):Number and Copy Number of CD19 CAR-γδT cells [Срок оценки: 12 months]
• PK: Persistence of CD19 CAR-γδT [Срок оценки: 12 months]
• PD(Pharmacodynamics) ：Changes in Various Cytokine Levels (IL-2, IL-4, IL-6, IFN-γ, TNF α, etc.) from Baseline [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age > 14 years, gender unrestricted;
• Clinically diagnosed with relapsed/refractory acute B-lymphoblastic leukemia, with bone marrow blast/immature lymphocyte proportion ≥5% (morphology) (excluding cases with isolated extramedullary involvement), meeting any of the following criteria:

• Failure to achieve CR after 2 cycles of standard chemotherapy;
• Initial induction achieved CR, but CR duration ≤12 months;
• Relapsed/refractory B-ALL refractory to first or multiple salvage therapies;
• Post-hematopoietic stem cell transplantation relapse, including hematological relapse and minimal residual disease (MRD) positivity;
• Patients for whom no standard therapy exists.
• Cytology or histology confirms tumor cell immunophenotype as CD19-positive;
• Expected survival time exceeding 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
• Key organ functions meeting the following criteria: left ventricular ejection fraction ≥50% by echocardiography; serum creatinine ≤1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × ULN; total bilirubin ≤1.5 × ULN;
• Negative pregnancy test for women of childbearing potential; both males and females agree to use effective contraception during treatment and for 1 year thereafter;
• Toxicity from prior anti-tumor therapy ≤ Grade 1 (according to CTCAE v5.0) or at an acceptable level per inclusion/exclusion criteria;
• No significant hereditary diseases;
• Able to comprehend the trial requirements and procedures, and willing to participate in the clinical study as required;
• Signed informed consent form for the trial

Критерии исключения

• Presence of central nervous system (CNS) involvement or a clinically significant history of CNS diseases, such as epilepsy and cerebrovascular diseases;
• Pregnant or lactating women, or women who disagree to use effective contraception during treatment and within 1 year after treatment;
• Other malignancies that are not in remission;
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
• Patients who have received allogeneic immune cell therapy within 6 months before enrollment, or donor lymphocyte infusion within 6 weeks before enrollment;
• Confirmed positive anti-FMC63 and DSA responses in the patient's serum;
• Patients who have participated in other clinical trials within 4 weeks before enrollment;
• Uncontrolled infectious diseases or other serious conditions, including but not limited to infections (human immunodeficiency virus, acute or chronic active hepatitis B or C), congestive heart failure, unstable angina, arrhythmia, or conditions considered by the treating physician to pose unpredictable risks;
• History of stroke or intracranial hemorrhage within 3 months before enrollment;
• Major surgery or trauma within 28 days before enrollment, or main side effects not yet recovered;
• History of allergy to any component of the cell product;
• Inability to understand or unwillingness to sign the informed consent form;
• Other reasons deemed by the researchers as unsuitable for the clinical trial.

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

• The first affiliated hospital of fujian medical university — Фучжоу

Идентификаторы

NCT: NCT07491263 · QH10309-NHB-01（0）

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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