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

Overview

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.

Interventions

• Biological 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).
• Drug 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).
• Drug 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).

Primary outcome measures

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

Secondary outcome measures (9)

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

Eligibility criteria

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)

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Fujian Medical University — Quanzhou

Identifiers

NCT: NCT07367685 · QH10309-NHB-01（0）

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗