Clinical Study of Universal CD19 CAR-γδT Cell Injection in the Treatment of Adult Relapsed/Refractory B-cell Lymphoma

Обзор

This study is an open-label, single-arm clinical trial designed to evaluate the safety and tolerability of QH103 cell injection solution in adult subjects with relapsed/refractory CD19-positive B-cell lymphoma.

Вмешательства

• Биопрепарат QH103 Cell Injection
  Biological: CD 19-CAR T cell Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with dose escalation (3+3) : dose 1 (3×10\^8 CAR+cells) ,dose 2 (6× 10\^8 CAR+cells).
• 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).

Первичные конечные точки

• Adverse Event [Срок оценки: 12months]
• Incidence of Dose-Limiting Toxicities (DLTs) [Срок оценки: First infusion date of QH103 cells to 28 days end cell infusion]
• Maximum tolerated dose (MTD) [Срок оценки: 28 days]

Вторичные конечные точки (9)

• PK-Tmax [Срок оценки: 12 months]
• Pharmacodynamics: Peak level of cytokines in serum [Срок оценки: 12 months]
• Overall Response Rate(ORR) [Срок оценки: 6 months]
• Overall Survival（OS） [Срок оценки: 6 months&12 months]
• Progression-Free Survival（PFS） [Срок оценки: 6 months]
• PK-Cmax [Срок оценки: 12 months]
• PK-AUC [Срок оценки: 12 months]
• PK-Tlast [Срок оценки: 12 months]
• PK-Clast [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age ≥ 18 years, no gender restrictions;
• Clinically diagnosed with relapsed/refractory B-cell lymphoma, malignant B- cell lymphoma (according to the Lugano (2014) criteria, with at least one evaluable tumour lesion, defined as: Lymph node lesions with a longest diameter exceeding 1.5 cm, or extranodal lesions with a longest diameter exceeding 1.0 cm), including diffuse large B-cell lymphoma (DLBCL-NOS), encompassing activated B-cell (ABC)/grossly centre B-cell (GCB) subtypes, primary mediastinal (thymic) large B-cell lymphoma (PMBCL), transformative follicular lymphoma (TFL), high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements,follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL)

• Relapsed B-cell lymphoma is defined as disease progression following ≥2 systemic therapies;
• Refractory disease is defined as failure to achieve complete remission (CR) on first-line therapy, or best response to first-line therapy being disease progression (PD), or best response after at least 4 cycles of first-line therapy being stable disease (SD)(e.g., 4 cycles of R-CHOP), or best response after at least 6 cycles being partial remission (PR) with biopsy-confirmed residual disease or disease progression within ≤6 months of treatment.
• Cytologically or histologically confirmed CD19-positive tumour cell immunophenotyping;
• Expected survival exceeding 3 months;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
• Major organ function meeting the following criteria: Echocardiogram showing left ventricular ejection fraction ≥50%; serum creatinine ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 3 × ULN; total bilirubin ≤ 1.5 × ULN;
• Negative pregnancy test for women of childbearing potential; both male and female subjects must agree to use effective contraception during treatment and for 1 year thereafter;
• Toxicity from prior antineoplastic therapy ≤ Grade 1 (per CTCAE version 5.0) or acceptable to the inclusion/exclusion criteria;
• No significant hereditary disorders;
• Ability to comprehend trial requirements and procedures, with willingness to participate in the clinical study as directed;
• Signing of the trial informed consent form.

Exclusion Criteria：

• Presence of central nervous system (CNS) involvement or clinically significant history of CNS disorders, such as epilepsy and cerebrovascular disease;
• Pregnant or lactating women, or women unwilling to use effective contraception during treatment and for 1 year post-treatment;
• Unremitted other malignancies;
• Patients with primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy;
• Patients who received allogeneic immune cell therapy within 6 months prior to enrolment, or donor lymphocyte infusion within 6 weeks prior to enrolment;
• Confirmed serum reactivity positive for anti-FMC63 and DSA;
• Patients participating in other clinical trials within 4 weeks prior to enrolment;
• 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 pectoris, arrhythmias, or conditions deemed to pose unpredictable risks by the treating physician;
• History of stroke or intracranial haemorrhage within 3 months prior to enrolment;
• Major surgery or trauma within 28 days prior to enrolment, or unresolved significant adverse events;
• History of allergy to any component of the cell product;
• Inability to comprehend or unwillingness to sign the informed consent form;
• Other reasons deemed by the investigator to render the patient 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 Second Affiliated Hospital of Fujian Medical University — Quanzhou

Идентификаторы

NCT: NCT07367685 · QH10309-NHB-01（0）

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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