CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL

Ningbo No. 1 Hospital

Status and phase

Enrolling

Phase 1

Conditions

Diffuse Large B-cell Lymphoma

Treatments

Combination Product: CD19-7×19 CAR-T combined with Tislelizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT05659628

Ningbo101

Details and patient eligibility

About

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.

Enrollment

24 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥ 18, upper limit 75, male or female;
ECOG score 0-3;
Histologically confirmed diffuse large B-cell lymphoma (DLBCL) [diagnostic criteria according to WHO 2008];
CD19 positive (immunohistochemistry or flow cytometry).
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;
Previous treatment for patients with diffuse large B cell lymphoma must include rituximab (CD20 monoclonal antibody) and anthracyclines;
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);
Absolute value of peripheral blood neutrophils ≥ 1000/ μ l. Platelets ≥ 45000/ μ l
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%;
Have sufficient understanding and voluntarily sign the informed consent form;
People with fertility must be willing to use contraceptive methods;
According to the judgment of the researcher, the expected survival period is at least 4 months;
Willing to follow the visit schedule, administration plan, laboratory inspection and other test steps.

Exclusion criteria

Have a history of other tumors;
Autologous hematopoietic stem cell transplantation was performed within 6 weeks;
Any target CAR-T treatment was performed within 3 months before this CAR-T treatment;
Previously used any commercially available PD-1 monoclonal antibody;
Cytotoxic drugs, glucocorticoids and other targeted drugs were received within 2 weeks before cell collection;
Active autoimmune diseases;
Uncontrollable active bacterial and fungal infections;
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.
Known central nervous system lymphoma.