Cytoplasmic Activated PD-1 CAR T Cells in Refractory/Relapsed B Cell Lymphoma

Phase 1

• Conditions: Relapsed Non Hodgkin Lymphoma
• Interventions: Drug: CAR19 T cells carrying cytoplasmic activated PD-1

• Registration Number: NCT03540303
• Lead Sponsor: Henan Cancer Hospital

Brief Summary

Evaluation of the safety and efficacy of CAR19 T cells carrying cytoplasmic activated PD1 in patients with refractory relapsed B-cell lymphoma

Detailed Description

Although CAR19 T cell therapy brings hope, the patients with refractory/relapsed B-cell lymphoma is still a problem for the current treatment. There are still some patients with poor therapeutic efficacy, and the efficacy of CAR19-T cell therapy remains to be improved. Basic research shows that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. However, the regimen of CAR19-T cells combined anti-PD1 inhibitors need to be combined with the application of anti-PD1 antibody and culture of CART cells during the treatment, there may be adverse events to PD1 antibodies. In this study, CAR19T cells carrying cytosolic activated PD1 possess the dual effects of CAR19T cells and anti-PD1 or anti-PD-L1 antibodies while overcoming the adverse events of anti-PD1 inhibitors, and might have better efficacy than conventional CAR19T cells plus anti-PD1 or anti-PD-L1 antibody treatment, with fewer side effects.

Study Timeline

• Status Verified: 2018-04
• Study Start: 2018-04-12
• Study First Submitted: 2018-05-16
• Study First Submitted QC: 2018-05-29
• Last Update Submitted: 2018-05-29
• Study First Posted: 2018-05-30
• Last Update Posted: 2018-05-30
• Primary Completion: 2020-04-30
• Study Completion: 2020-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• 18-70 years old and the expected lifetime >3 months
• Refractory/relapsed CD19 positive B cell lymphoma by pathology
• ECOG score <2
• Measureable lesions according to RECIST 1.1
• Sufficient heart, liver, kidney and bone marrow function (heart: no heart disease or coronary heart disease, patient heart function NYHA grade 1-2; liver: TBIL ≤ 3ULN, AST ≤ 2.5ULN, ALT ≤ 2.5ULN; kidney: Cr≤ 1.25ULN; bone marrow: WBC ≥ 2.0 × 109/L, Hb ≥ 80 g/L, PLT ≥ 30 × 109/L)
• no serious allergies
• No other serious diseases that conflict with this protocol (eg, autoimmune diseases, immunodeficiency, organ transplantation)
• No other history of malignancy
• No serious mental disorders
• Women of childbearing age must be negative for blood pregnancy test within 7 days and must take appropriated contraceptive measures during and 3 months after the study
• The patient himself agrees to participate in this clinical study and signed the "informed consent"

Exclusion Criteria

• Lactating women
• Severe infectious or viral diseases (HIV positive, syphilis, etc.)
• Active hepatitis B or C viral hepatitis
• Patients who used high-dose glucocorticoids within 1 week
• Participation in other clinical studies in the past 3 months or having been treated with other gene products

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CAR19 T cells carrying cytoplasmic activated PD-1	CAR19 T cells carrying cytoplasmic activated PD-1	patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells.

Primary Outcome Measures

Name	Time	Method
safety: occurrence of study related adverse events	6 months	occurrence of study related adverse events

Secondary Outcome Measures

Name	Time	Method
objective response rate	3 months and 6 months	tumor burdens shrink more than 30 percent by RECIST1.1

Trial Locations

Locations (1)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China