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

NCT05659628 | Recruiting Phase 1

• 1 other identifier: Ningbo101
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Progress free survival time

  up to 24 months

• Overall survival

  up to 24 months

Study Arms (1)

CAR-T combined with anti-PD1 treatment group

EXPERIMENTAL

CD19-7×19 CAR-T combined with Tislelizumab

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

Interventions

CD19-7×19 CAR-T combined with Tislelizumab COMBINATION_PRODUCT

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.

CAR-T combined with anti-PD1 treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ningbo No. 1 Hospital: lead
• Zhejiang University: collaborator

Study Sites (2)

The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital

Hangzhou, Zhejiang, 310009, China

RECRUITING

Ningbo First Hospital

Ningbo, Zhejiang, 315010, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

tislelizumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Lixia Sheng, doctor

CONTACT

86-574-87085596; slx800408@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2022
• First Posted: December 21, 2022
• Study Start: December 1, 2022
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 21, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)