Recurrent/Refractory B-cell Lymphoma
Conditions
Keywords
CD19, CAR-γδT, cell therapy
Brief summary
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
BIOLOGICALQH103 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).
DRUGCyclophosphamide
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).
DRUGFludarabine
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).
Sponsors
The Second Affiliated Hospital of Fujian Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | 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) | 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) | 28 days | MTD is defined as the highest dose level of less than or equal to 2 DLT among the 6 subjects finally determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK-Tmax | 12 months | Time to peak in CAR-T cell count in peripheral blood after infusion of QH103. |
| Pharmacodynamics: Peak level of cytokines in serum | 12 months | The Changes from baseline of level cytokines and chemokines in peripheral blood after infusion of QH103 |
| Overall Response Rate(ORR) | 6 months | Defined as complete response plus partial response. |
| Overall Survival（OS） | 6 months&12 months | Survival as estimated by Kaplan-Meier method. Death from any cause is considered as event for analysis. |
| Progression-Free Survival（PFS） | 6 months | Survival as estimated by Kaplan-Meier method. The length of time during and after the treatment of a disease is considered as event for analysis. |
| PK-Cmax | 12 months | Peak concentration (Cmax) in the CAR-T cell count in peripheral blood after infusion of QH103. |
| PK-AUC | 12 months | Area under the concentration-time curve of CAR-T cell count in peripheral blood after infusion of QH103 from 0 to 12 months |
| PK-Tlast | 12 months | The final time point in CAR-T cell count in peripheral blood after infusion of QH103. |
| PK-Clast | 12 months | The final point concentration (C last) in the CAR-T cell count in peripheral blood after infusion of QH103 |
Countries
China
Contacts
CONTACTJianda Hu
Outcome results
None listed