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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Adverse events profile [Time frame: Measured from start of treatment until 28 days after last dose.]
• Objective Response Rate [Time frame: up to 3 months]

Secondary outcome measures (2)

• Progress free survival time [Time frame: up to 24 months]
• Overall survival [Time frame: up to 24 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• The Second Affiliated Hospital of Zhejiang University, Ningbo First Hospital — Hangzhou
• Ningbo First Hospital — Ningbo

Identifiers

NCT: NCT05659628 · Ningbo101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗