Diffuse Large B-cell Lymphoma
Conditions
Brief summary
The goal of this clinical trial is to test CD19-7×19 CAR-T cells combined with Tislelizumab in refractory and relapsed diffuse large B lymphoma. The main question\[s\] it aims to answer are: question 1：What is the safety of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. question 2：What is the efficacy of CD19-7×19 CAR-T cells combined with Tislelizumab in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Participants will be asked to receive clinical evaluation before CAR-T, including physical examination, blood routine test, biochemical test, imaging test, etc.Peripheral blood lymphocytes will be collected for preparation of CAR-T cells after enrollment. Pretreatment chemotherapy with fludarabine and cyclophosphamide will be used before CAR-T infusion. On the 31st day after CAR-T infusion, Tislelizumab 200mg was given once every 21 days for 6 cycles. Participants will be required to report concomitant medication and adverse events, and their disease was evaluated throughout the study.
Interventions
COMBINATION_PRODUCTCD19-7×19 CAR-T combined with Tislelizumab
Participants will receive 2×106/Kg CD19-7×19 CAR-T cells infusion and Tislelizumab 200mg every 21 days for 6 cycle on the 31st day after CAR-T infusion.
Sponsors
Zhejiang University
Ningbo No. 1 Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events profile | Measured from start of treatment until 28 days after last dose. | Number of participants with adverse events. Frequencies of toxicities based on the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 will be tabulated. |
| Objective Response Rate | up to 3 months | Proportion of CR and PR subjects will be assessed at 3 months post-infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progress free survival time | up to 24 months | To measure the duration of response over a follow-up period of 24 months. |
| Overall survival | up to 24 months | OS will be assessed from the first chimeric antigen receptor T cells (CAR-T) given to death or last follow-up. |
Countries
China
Contacts
Primary ContactLixia Sheng, doctor
Outcome results
None listed