B Cell Lymphoma
Conditions
Keywords
ssCART-19, Relapsed or Refractory B-Cell Lymphma, IL-6
Brief summary
This is an open-label phase1 study to assess the safety and efficacy of U01(ssCART-19) cell therapy in the treatment of patients with refractory or recurrent B-cell lymphoma .
Detailed description
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are critical complications in CAR T-cell therapy. Research highlights IL-6 as a central driver of CRS, as activated CAR T-cells secrete this cytokine, which in turn stimulates monocytes to produce additional IL-6. To mitigate this risk, ssCART-19-a modified anti-CD19 CAR T-cell therapy-incorporates small hairpin RNA (shRNA) technology to silence the IL-6 gene, thereby reducing IL-6 secretion by both CAR T-cells and monocytes. This study aims to assess the safety and efficacy of the U01 (ssCART-19) therapy in patients with refractory or recurrent B-cell lymphoma .
Interventions
BIOLOGICALssCART-19
autologous T cells transduced with a lentiviral vector containing anti-CD19 CAR and small hairpin RNA to silence the IL-6 gene
Sponsors
Shanghai Tongji Hospital, Tongji University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must voluntarily sign the informed consent form (ICF) and demonstrate good compliance. 2. Participants must meet the following requirements: 1. Age ≥2 years and ≤75 years at the time of signing the ICF (both sexes eligible). For minors (\<18 years), the legal guardian must sign after full disclosure; minors with decision-making capacity must co-sign with their guardians. 2. Confirmed diagnosis of B-cell lymphoma according to the NCCN Clinical Practice Guidelines for B-Cell Lymphomas (3rd Edition, 2024) . 3. Prior treatment requirements : Failure to achieve partial response (PR) after first-line therapy, or relapse within 12 months post-first-line therapy; Relapsed/refractory B-cell lymphoma after second-line therapy (one standard chemotherapy regimen + one salvage regimen). Prior treatments must include CD20 monoclonal antibody (unless CD20-negative tumor confirmed by the investigator) and anthracycline-based regimens . Additionally, meet one of the following: i. Ineligible for autologous stem cell transplantation (ASCT); ii. Refusal of ASCT; iii. Post-ASCT relapse. d) Refractory/relapsed status at screening: Relapse: Disease progression (PD) after achieving PR or complete response (CR); Refractory: i. No response to last-line therapy (PD during/after treatment, or stable disease \[SD\] lasting \<6 months); ii. Post-ASCT relapse/PD (biopsy-confirmed), including relapse/PD within 12 months post-ASCT with SD/PD after salvage therapy2. 3. CD19 positivity confirmed by immunohistochemistry (IHC) of tumor tissue (preferably within 6 months). 4. At least one measurable lesion assessed by the Lugano Lymphoma Response Criteria (Cheson 2014) . 5. ECOG performance status score 0-3 . 6. Adequate bone marrow reserve at screening: Absolute lymphocyte count (ALC) ≥0.3×10⁹/L ; Platelet count (PLT) ≥30×10⁹/L . 7. Adequate organ function: AST/ALT ≤3×ULN (≤5×ULN if due to tumor infiltration); Total bilirubin ≤2×ULN (≤3×ULN for Gilbert syndrome with direct bilirubin ≤1.5×ULN); Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); Oxygen saturation \>91% on room air (dyspnea grade ≤1); Left ventricular ejection fraction (LVEF) ≥50% ; INR ≤1.5×ULN and APTT ≤1.5×ULN . 8. Negative pregnancy test (blood/urine) within 7 days before CAR-T infusion for women of childbearing potential. All participants must agree to use effective contraception during the study and for ≥1 year post-treatment. 9. Adequate venous access for leukapheresis or blood collection, with no contraindications to leukapheresis. 10. Expected survival ≥3 months .
Exclusion criteria
1. Concurrent malignancies , except for: Malignancies with disease-free survival (DFS) \>3 years ; Carcinoma in situ ; 2. Active viral infections : Hepatitis B : Positive for HBe-Ab and/or HBc-Ab with HBV-DNA \> lower limit of quantitation (LLOQ) ; Hepatitis C : Positive HCV-Ab with HCV-RNA \> LLOQ ; Positive Treponema pallidum antibody (TP-Ab); Positive HIV antibody ; 3. Uncontrolled infections (bacterial, fungal, viral, mycoplasmal, or others) as determined by the investigator; 4. Clinically significant CNS diseases (current or history), including: Epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disorders, or CNS-related autoimmune diseases , deemed uncontrolled by the investigator; 5. Cardiovascular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate(ORR) | At 1,3,6,9,12,18 and 24 months post-treatment follow up | — |
| Progression free survival(PFS) | At 1,3,6,9,12,18 and 24 months post-treatment follow up | — |
| Overall survival(OS) | At 1,3,6,9,12,18 and 24 months post-treatment follow up | — |
| The types, frequency, and severity of treatment related adverse events | Day1 to Week 4 | After CAR-T cell infusion, we will observe the potential adverse events, especially Cytokine Release Syndrome(CRS) and neurotoxicity Using NCI Common Terminology Criteria for Adverse Events(CTCAE) V5.0 |
| Duration of response (DOR) | At 1,3,6,9,12,18 and 24 months post-treatment follow up | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Monitoring changes in IL-6, ferritin, and CRP in peripheral blood following CAR-T cell infusion | Day1 to Month 3 | — |
| Kinetics of CAR-T cells | Day1 to Month 3 | Use flow cytometry or qPCR to monitor the kinetics of CAR-T cells |
Countries
China
Contacts
Primary ContactWenjun Zhang, Doctor
Outcome results
None listed