CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* 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)

  1. Relapsed B-cell lymphoma is defined as disease progression following ≥2 systemic therapies;
  2. 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.

主要终点：Adverse Event · 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 · 12months；Incidence of Dose-Limiting Toxicities (DLTs) · DLT was defined as QH103 Cells-related events with onset within first 28 days following infusion. · First infusion date of QH103 cells to 28 days end cell infusion；Maximum tolerated dose (MTD) · MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined. · 28 days
次要终点：PK-Tmax；Pharmacodynamics: Peak level of cytokines in serum；Overall Response Rate(ORR)；Overall Survival（OS）；Progression-Free Survival（PFS）；PK-Cmax；PK-AUC；PK-Tlast

• Adult patients with relapsed/refractory CD19-positive B-cell lymphoma · EXPERIMENTAL · 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

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.