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

Primary Purpose

Relapsed Non Hodgkin Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

CAR19 T cells carrying cytoplasmic activated PD-1

About this trial

This is an interventional treatment trial for Relapsed Non Hodgkin Lymphoma focused on measuring relapsed/refractory, B cell, lymphoma, CAR

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Henan Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR19 T cells carrying cytoplasmic activated PD-1

Arm Description

patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells.

Outcomes

Primary Outcome Measures

safety: occurrence of study related adverse events

occurrence of study related adverse events

Secondary Outcome Measures

objective response rate

tumor burdens shrink more than 30 percent by RECIST1.1

Full Information

NCT ID

NCT03540303

First Posted

May 16, 2018

Last Updated

May 29, 2018

Sponsor

Henan Cancer Hospital

Collaborators

The Pregene (ShenZhen) Biotechnology Company, Ltd.

1. Study Identification

Unique Protocol Identification Number

NCT03540303

Brief Title

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

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Unknown status

Study Start Date

April 12, 2018 (Actual)

Primary Completion Date

April 30, 2020 (Anticipated)

Study Completion Date

April 30, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Henan Cancer Hospital

Collaborators

The Pregene (ShenZhen) Biotechnology Company, Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed Non Hodgkin Lymphoma

Keywords

relapsed/refractory, B cell, lymphoma, CAR

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

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.

Masking

None (Open Label)

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CAR19 T cells carrying cytoplasmic activated PD-1

Arm Type

Experimental

Arm Description

patients with refractory/relapsed B-NHL receive a preconditioning before infusion of CAR T cells.

Intervention Type

Drug

Intervention Name(s)

CAR19 T cells carrying cytoplasmic activated PD-1

Intervention Description

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.

Primary Outcome Measure Information:

Title

safety: occurrence of study related adverse events

Description

occurrence of study related adverse events

Time Frame

6 months

Secondary Outcome Measure Information:

Title

objective response rate

Description

tumor burdens shrink more than 30 percent by RECIST1.1

Time Frame

3 months and 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Yongping Song, M.D

Phone

+86-371-65587199

songyongping2018@126.com

First Name & Middle Initial & Last Name or Official Title & Degree

Quanli Gao, M.D

Phone

+86-15038171966

gaoquanli2015@126.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yongping Song, M.D

Organizational Affiliation

Henan Cancer Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Henan Cancer Hospital

City

Zhengzhou

State/Province

Henan

ZIP/Postal Code

450000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Quanli Gao, M.D

Phone

+86-15038171966

gaoquanli2015@126.com

First Name & Middle Initial & Last Name & Degree

Lu Han, M.D

Phone

+86-13838583031

luhan0377@163.com

12. IPD Sharing Statement

Learn more about this trial

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

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