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

Overview

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

• Biological ssCART-19
  autologous T cells transduced with a lentiviral vector containing anti-CD19 CAR and small hairpin RNA to silence the IL-6 gene

Primary outcome measures

• The types, frequency, and severity of treatment related adverse events [Time frame: Day1 to Week 4]
• Objective response rate(ORR) [Time frame: At 1,3,6,9,12,18 and 24 months post-treatment follow up]
• Duration of response (DOR) [Time frame: At 1,3,6,9,12,18 and 24 months post-treatment follow up]
• Progression free survival(PFS) [Time frame: At 1,3,6,9,12,18 and 24 months post-treatment follow up]
• Overall survival(OS) [Time frame: At 1,3,6,9,12,18 and 24 months post-treatment follow up]

Secondary outcome measures (2)

• Kinetics of CAR-T cells [Time frame: Day1 to Month 3]
• Monitoring changes in IL-6, ferritin, and CRP in peripheral blood following CAR-T cell infusion [Time frame: Day1 to Month 3]

Eligibility criteria

Inclusion criteria

• Participants must voluntarily sign the informed consent form (ICF) and demonstrate good compliance.
• Participants must meet the following requirements:

• 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.
• Confirmed diagnosis of B-cell lymphoma according to the NCCN Clinical Practice Guidelines for B-Cell Lymphomas (3rd Edition, 2024) .
• 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.

• CD19 positivity confirmed by immunohistochemistry (IHC) of tumor tissue (preferably within 6 months).
• At least one measurable lesion assessed by the Lugano Lymphoma Response Criteria (Cheson 2014) .
• ECOG performance status score 0-3 .
• Adequate bone marrow reserve at screening:

Absolute lymphocyte count (ALC) ≥0.3×10⁹/L ; Platelet count (PLT) ≥30×10⁹/L .

• 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 .

• 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.
• Adequate venous access for leukapheresis or blood collection, with no contraindications to leukapheresis.
• Expected survival ≥3 months .

Exclusion criteria

• Concurrent malignancies , except for:

Malignancies with disease-free survival (DFS) >3 years ; Carcinoma in situ ;

• 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 ;

• Uncontrolled infections (bacterial, fungal, viral, mycoplasmal, or others) as determined by the investigator;
• 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;

• 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;

• Primary immunodeficiency ;
• Severe immediate hypersensitivity to any study drug;
• Live vaccine administration within 6 weeks prior to screening ;
• Pregnancy or lactation ;
• Active autoimmune diseases ;
• Participation in another interventional clinical trial within 30 days prior to ICF signing ;
• Other conditions deemed ineligible by the investigator.

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

• Shanghai Tongji Hospital ( Tongji Hospital of Tongji University) — Shanghai

Identifiers

NCT: NCT06987916 · U01-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗