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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Combination product: CD19-7×19 CAR-T combined with Tislelizumab

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lixia Sheng, doctor; Phone Number: 86-574-87085596; Email: slx800408@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital
      • Contact: Wenbin Qian, Doctor; Phone Number: 86-571-87581969; Email: qianwb@zju.edu.cn
    • Ningbo, Zhejiang, China, 315010
      • Recruiting
      • Ningbo First Hospital
      • Contact: Lixia Sheng, doctor; Phone Number: 86-574-87085596; Email: slx800408@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T combined with anti-PD1 treatment group; CD19-7×19 CAR-T combined with Tislelizumab	Combination product: CD19-7×19 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events profile	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.	Measured from start of treatment until 28 days after last dose.
Objective Response Rate	Proportion of CR and PR subjects will be assessed at 3 months post-infusion.	up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress free survival time	To measure the duration of response over a follow-up period of 24 months.	up to 24 months
Overall survival	OS will be assessed from the first chimeric antigen receptor T cells (CAR-T) given to death or last follow-up.	up to 24 months

Collaborators and Investigators

• Sponsor: Ningbo No. 1 Hospital
• Collaborators: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: November 26, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Estimate): December 21, 2022

Study Record Updates

• Last Update Posted (Estimate): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: Ningbo101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No