Safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory B cell lymphoma 

The PD1 pathway is critical in determining the response to CAR T cell therapy. New data suggested that inhibition of PD1 could improve the efficacy of CAR T cell therapy. iPD1 CD19 eCAR T cells are an enhanced version of the classical second-generation anti-CD19 4-1BB-assisted stimulatory chimeric antigen receptor-engineered T cells with intracellular PD1 inhibition by binding the PD1 shRNA expression cassette to the CAR lentivector. This approach will improve the antitumor activity of CAR T cells by inhibiting PD1 induction after CAR T cell activation. This pilot, single cancer, single center, dose escalation, and open study is to determine the safety and efficacy of iPD1 CD19 eCAR T cells in relapsed or refractory CD19 positive lymphomas.

Patients will be given lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide prior to CAR T cell injection. Chemotherapy is completed 1 to 4 days before the first dose of iPD1 CD19 eCAR T cells.

Clinical Overview

 - Target disease: Recurrent or intractable B cell lymphoma 

 - Intervention / treatment: iPD1 CD19 eCAR T cells 

 - Phase: 1 phase 

 - Drugs: Fludarabine and cyclophosphamide 

 - Target age: 18 to 70 years old (adult, elderly) 

 - Target gender: All 

 - Applicant health status: irrelevant 

Include by:

 - confirmed by CD19 + B cell lymphoma, IHC or flow cytometry. 

 - The history of at least one standard therapy. 

 - Not suitable for allograft or recurrence after transplantation. 

 - The patient is over 18 years old. 

 - Those whose life expectancy is more than 3 months 

 - ECOG ≤ 2. 

 - satisfactory major organ function: adequate cardiac function with LVEF≥50%; More than 90% pulse oximetry; Cockcroft - Graft creatinine clearance ≥ 40 ml / min; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3ULN; Bilirubin ≤ 2.0 mg / dl. 

 - Blood: Hgb ≥ 80 g / L, ANC ≥ 1 x 10 ^ 9 / L, PLT ≥ 50 x 10 ^ 9 / L. 

 - Women with potential for reproduction should undergo a negative pregnancy test. Female and male females should agree to use contraception for the duration of the study and for one year of study. 

 - measurable tumor 

By exclusion:

 - Immunosuppressive drugs or systemic steroids within one week of enrollment 

 - Infection with active disease 

 - HIV positive 

 - active hepatitis B virus infection or hepatitis C virus infection. 

 - Breastfeeding or pregnant women. 

 - Patients with previous malignant tumors who were excluded from the study but who were treated with skin basal cell carcinoma or cervical cancer, or who underwent surgical resection to remove the tumor but had tumors without further treatment and survived for years after 5 years of age Can be included in research 

 - Currently participating in other studies 

 - Patient may be disqualified in the opinion of examiner