Clinical trial NCT03540303: Cytoplasmic Activated PD-1 CAR T Cells in Refractory/Relapsed B Cell Lymphoma
Official title: Phase Ⅰ Study of CAR19 T Cells Carrying Cytoplasmic Activated PD-1 in the Treatment of Refractory/Relapsed B Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Relapsed Non Hodgkin Lymphoma
Keywords: relapsed/refractory, B cell, lymphoma, CAR
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
Collaborators: name: The Pregene (ShenZhen) Biotechnology Company, Ltd.
First posted: 2018-05-30
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention model description: CAR19 T cell therapy improves the clinical efficacy of refractory/relapsed B-cell lymphoma, and the combined PDL1 inhibitors may further improve the efficacy of CD19 CART in the treatment of lymphomas. The clinical efficacy of KITE's CAR19 T cells and PD-L1 inhibition was reported. This phase 1 study was conducted in 9 patients with DLBCL, 8 patients got remission and during which 5 got complete remission. However, this type of treatment requires more data and observation in a larger sample of patients. In addition, Kite Pharmaceuticals' CD19 CART is priced at 370,000 US dollars. The cost of immune checkpoint inhibitors is also very expensive. Only very small proportion of patients could afford for that expenses. In this study, genetically engineered CAR T cells, which carry cytoplasmic activated PD1, are not inhibited by PDL1 molecules, will avoid the simultaneous application of immune checkpoint antibodies and the according adverse events.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: safety: occurrence of study related adverse events
timeFrame: 6 months
Secondary outcomes:
measure: objective response rate
timeFrame: 3 months and 6 months
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Yongping Song, M.D
role: STUDY_CHAIR
References: