Clinical Study of Universal CD19 CAR-γδT Cell Injection in the Treatment of Adult Relapsed/Refractory B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Adverse Event
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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/
排除标准
- •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.
研究组 & 干预措施
Adult patients with relapsed/refractory CD19-positive B-cell lymphoma
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
Interventions:
Biological: QH103 Cell Injection Drug: Fludarabine Drug: Cyclophosphamide
干预措施: QH103 Cell Injection (Biological)
Adult patients with relapsed/refractory CD19-positive B-cell lymphoma
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
Interventions:
Biological: QH103 Cell Injection Drug: Fludarabine Drug: Cyclophosphamide
干预措施: Cyclophosphamide (Drug)
Adult patients with relapsed/refractory CD19-positive B-cell lymphoma
A conditional chemotherapy regimen of fludarabine and cyclophosphamide will be administered, followed by investigational therapy, QH103 Cells
Interventions:
Biological: QH103 Cell Injection Drug: Fludarabine Drug: Cyclophosphamide
干预措施: Fludarabine (Drug)
结局指标
主要结局
Adverse Event
时间窗: 12months
AE is defined as any adverse medical event from the date of leukapheresis to 12 months after QH103 infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versushost disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: First infusion date of QH103 cells to 28 days end cell infusion
DLT was defined as QH103 Cells-related events with onset within first 28 days following infusion.
Maximum tolerated dose (MTD)
时间窗: 28 days
MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined.
次要结局
- PK-Tmax(12 months)
- Pharmacodynamics: Peak level of cytokines in serum(12 months)
- Overall Response Rate(ORR)(6 months)
- Overall Survival（OS）(6 months&12 months)
- Progression-Free Survival（PFS）(6 months)
- PK-Cmax(12 months)
- PK-AUC(12 months)
- PK-Tlast(12 months)
- PK-Clast(12 months)
研究者
Meiling Li
The Chief of the Department of Hematology
The Second Affiliated Hospital of Fujian Medical University