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

• Sponsor: Ningbo No. 1 Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05659628
• Collaborator: Zhejiang University (Other)
• Enrollment: 24
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 48
• Patients Per Site: 12
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Combination Product: CD19-7×19 CAR-T combined with Tislelizumab	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Dec 1, 2022
• Anticipated Primary Completion Date: Dec 1, 2024
• Anticipated Study Completion Date: Dec 1, 2026

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. Objective Response Rate [up to 3 months]

   Proportion of CR and PR subjects will be assessed at 3 months post-infusion.

Secondary Outcome Measures

1. Progress free survival time [up to 24 months]

   To measure the duration of response over a follow-up period of 24 months.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital	Hangzhou	Zhejiang	China	310009
2	Ningbo First Hospital	Ningbo	Zhejiang	China	315010

Sponsors and Collaborators

• Ningbo No. 1 Hospital
• Zhejiang University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ningbo No. 1 Hospital
• ClinicalTrials.gov Identifier: NCT05659628
• Other Study ID Numbers: Ningbo101
• First Posted: Dec 21, 2022
• Last Update Posted: Dec 21, 2022
• Last Verified: Dec 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Dec 21, 2022