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

Phase Ⅰ Study of CAR19 T Cells Carrying Cytoplasmic Activated PD-1 in the Treatment of Refractory/Relapsed B Cell Lymphoma

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

Study Overview

• Status: Unknown
• Conditions: Relapsed Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: CAR19 T cells carrying cytoplasmic activated PD-1

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: CAR19 T cells carrying cytoplasmic activated PD-1; step 1: Collect 50-100ml of peripheral blood for culture of CAR19 T cells carrying cytoplasmic activated PD-1 step 2. After 72 hours, pretreated with FC regimen, details as follow Cyclophosphamide 600-800mg/m2 for 2 days Fludarabine 25-30mg/m2 for 3 days step 3: After another 48 hours transfusion the cells back to the patients the numbers of infused CAR T cells are 2x106 /kg for the first 3 patients, 6x106 /kg for the second 3 patients and 18x106 /kg for the third 3 patients. After finishing this, another 6 patients will be enrolled for observation of efficacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety: occurrence of study related adverse events	occurrence of study related adverse events	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	tumor burdens shrink more than 30 percent by RECIST1.1	3 months and 6 months

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Collaborators: The Pregene (ShenZhen) Biotechnology Company, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2018
• Primary Completion (Anticipated): April 30, 2020
• Study Completion (Anticipated): April 30, 2020

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: May 29, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Actual): May 30, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: relapsed/refractory, B cell, lymphoma, CAR
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: HenanCH CAR 2-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No