Treatment for relapsed or refractory diffuse large B-cell lymphoma using CAR-T cells and anti-PD1 therapy

Phase Ib Clinical Study of CD19 CAR-T Expressing IL-7 and CCL19 Combined With Tislelizumab in the Treatment of Relapsed/Refractory Diffuse Large B-cell Lymphoma

This study is testing a new treatment combining CAR-T cells and an immune therapy for people with relapsed or hard-to-treat diffuse large B-cell lymphoma to see if it helps them.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ningbo No. 1 Hospital (Academic / other)
• Drugs / interventions: rituximab, CAR-T, Tislelizumab, chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Hangzhou, Zhejiang and 1 other locations)
• Trial ID: NCT05659628 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and efficacy of CD19-7×19 CAR-T cells combined with Tislelizumab in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Participants will undergo a series of clinical evaluations and receive pretreatment chemotherapy before the CAR-T cell infusion. Following the infusion, Tislelizumab will be administered every 21 days for six cycles. The study will assess both the safety profile and the treatment outcomes of this combined approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed CD19 positive DLBCL that is refractory or has relapsed after previous treatments.

Not a fit: Patients who have not previously received rituximab or anthracyclines, or those with other types of lymphoma, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat DLBCL.

How similar studies have performed: Other studies have shown promising results with CAR-T cell therapies in similar patient populations, indicating potential for success with this novel combination approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18, upper limit 75, male or female;
2. ECOG score 0-3;
3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) \[diagnostic criteria according to WHO 2008\];
4. CD19 positive (immunohistochemistry or flow cytometry).
5. DLBCL refractory or relapse is defined as: complete remission is not achieved after 2-line treatment; let What disease progress occurs during treatment, or the disease stability time is equal to or less than 6 months; Or autologous hematopoietic stem Disease progression or recurrence within 12 months after cell transplantation;
6. Previous treatment for patients with diffuse large B cell lymphoma must include rituximab (CD20 monoclonal antibody) and anthracyclines;
7. At least one measurable lesion is required, and any lymph node lesion with a length greater than 1.5cm or extranodal lesion is required If any length diameter is greater than 1.0 cm, the lesions on PET-CT scan have uptake (SUV is larger than liver blood pool);
8. Absolute value of peripheral blood neutrophils ≥ 1000/ μ l. Platelets ≥ 45000/ μ l
9. Heart, liver and kidney functions: creatinine \< 1.5mg/dL; ALT/AST Less than 2.5 times of normal upper limit; Total bilirubin \< 1.5mg/dL; Cardiac ejection fraction (EF) ≥ 50%;
10. Have sufficient understanding and voluntarily sign the informed consent form;
11. People with fertility must be willing to use contraceptive methods;
12. According to the judgment of the researcher, the expected survival period is at least 4 months;
13. Willing to follow the visit schedule, administration plan, laboratory inspection and other test steps.

Exclusion Criteria:

1. Have a history of other tumors;
2. Autologous hematopoietic stem cell transplantation was performed within 6 weeks;
3. Any target CAR-T treatment was performed within 3 months before this CAR-T treatment;
4. Previously used any commercially available PD-1 monoclonal antibody;
5. Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection;
6. Active autoimmune diseases;
7. Uncontrollable active bacterial and fungal infections;
8. HIV infection and syphilis infection; Active hepatitis B or hepatitis C: hepatitis B: HBV-DNA ≥ 1000 IU/mL; Hepatitis C: HCV RNA is positive and liver function is abnormal.
9. Known central nervous system lymphoma.

Where this trial is running

Hangzhou, Zhejiang and 1 other locations

• The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital — Hangzhou, Zhejiang, China (Recruiting)
• Ningbo First Hospital — Ningbo, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Lixia Sheng, doctor

Conditions Diffuse Large B-cell Lymphoma