Clinical trial NCT05659628: CD19 CAR-T Expressing IL-7 and CCL19 Combined With Anti-PD1 in RR-DLBCL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Diffuse Large B-cell Lymphoma
Lead sponsor: Ningbo No. 1 Hospital
Sponsor class: OTHER
Collaborators: name: Zhejiang University
First posted: 2022-12-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Adverse events profile
timeFrame: Measured from start of treatment until 28 days after last dose.
measure: Objective Response Rate
timeFrame: up to 3 months
Secondary outcomes:
measure: Progress free survival time
timeFrame: up to 24 months
measure: Overall survival
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
Study officials:
References: