Clinical trial NCT06987916: Efficacy and Safety Evaluation of U01(ssCART-19) in B-Cell Lymphoma
Official title: A Single-Arm, Open-Label Clinical Study on the Efficacy and Safety of U01 (ssCART-19) in the Treatment of Relapsed or Refractory B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: B Cell Lymphoma
Keywords: ssCART-19
Relapsed or Refractory B-Cell Lymphma
IL-6
Lead sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine
Sponsor class: OTHER
First posted: 2025-05-23
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 .

Eligibility criteria: 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.

Primary outcomes:
measure: The types, frequency, and severity of treatment related adverse events
timeFrame: Day1 to Week 4
measure: Objective response rate(ORR)
timeFrame: At 1,3,6,9,12,18 and 24 months post-treatment follow up
measure: Duration of response (DOR)
timeFrame: At 1,3,6,9,12,18 and 24 months post-treatment follow up
measure: Progression free survival(PFS)
timeFrame: At 1,3,6,9,12,18 and 24 months post-treatment follow up
measure: Overall survival(OS)
timeFrame: At 1,3,6,9,12,18 and 24 months post-treatment follow up
Secondary outcomes:
measure: Kinetics of CAR-T cells
timeFrame: Day1 to Month 3
measure: Monitoring changes in IL-6, ferritin, and CRP in peripheral blood following CAR-T cell infusion
timeFrame: Day1 to Month 3
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tongji Hospital ( Tongji Hospital of Tongji University)
state: Shanghai
Study officials:
affiliation: Tongji hospital of tongji university (Shanghai tongji hospital)
name: Wenjun Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: