Efficacy and Safety Evaluation of U01(ssCART-19) in B-Cell Lymphoma

Phase 1

Recruiting

• Conditions: B Cell Non-Hodgkin&Amp;#39;s Lymphoma
• Interventions: Drug: ssCART-19

• Registration Number: NCT06987916
• Lead Sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine

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 refractory or recurrent DLBCL

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 diffuse large B-cell lymphoma (DLBCL).

Study Timeline

• Study Start: 2025-04-22
• Status Verified: 2025-05
• Study First Submitted: 2025-05-15
• Study First Submitted QC: 2025-05-15
• Last Update Submitted: 2025-05-15
• Study First Posted: 2025-05-23
• Last Update Posted: 2025-05-23
• Primary Completion: 2028-04-22
• Study Completion: 2030-04-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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 exclusion criteria :

   Cardiac angioplasty/stent placement within 12 months prior to signing ICF ; NYHA Class II-IV congestive heart failure , myocardial infarction, unstable angina, or other clinically significant cardiac history; QTe interval ≥480 ms (Fridericia correction) or LVEF <50% at screening;

6. Primary immunodeficiency ;

7. Severe immediate hypersensitivity to any study drug;

8. Live vaccine administration within 6 weeks prior to screening ;

9. Pregnancy or lactation ;

10. Active autoimmune diseases ;

11. Participation in another interventional clinical trial within 30 days prior to ICF signing ;

12. Other conditions deemed ineligible by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ssCART-19	ssCART-19	All enrolled patients in this arm will receive ssCART-19

Primary Outcome Measures

Name	Time	Method
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
Objective response rate(ORR)	At 1,3,6,9,12,18 and 24 months post-treatment follow up
Duration of response (DOR)	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

Secondary Outcome Measures

Name	Time	Method
Kinetics of CAR-T cells	Day1 to Month 3	Use flow cytometry or qPCR to monitor the kinetics of CAR-T cells
Monitoring changes in IL-6, ferritin, and CRP in peripheral blood following CAR-T cell infusion	Day1 to Month 3

Trial Locations

Locations (1)

Shanghai Tongji Hospital ( Tongji Hospital of Tongji University); 🇨🇳 Shanghai, China