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Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma

Primary Purpose

Lymphoma, B-Cell

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

CD19-PD1-CART Cell

About this trial

This is an interventional treatment trial for Lymphoma, B-Cell focused on measuring Lymphoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, Immunotherapy, PD-1, CD19

Eligibility Criteria

14 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, aged 14 to 80 years (including 14 and 80 years old).
The diagnosis was Refractory/relapsed B-cell lymphoma.(Meeting 1 of the first 4 items plus item 5)
A.Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy.
B.Achieved CR after standard chemotherapy, but relapsed within 6 months.
C.2 or more relapses after CR.
D.Not suitable for HSCT, or relapse after HSCT.
E.Subjects must have received adequate treatment in the past and the predicted survival is more than three months.
Patient or his or her legal guardian voluntarily participates in this stuy and signs an informed consent form.
Flow cytometry or immunohistochemistry showed CD19 positive in tumor cells.
No serious concomitant disease and major organ function is not serious abnormal.
ECOG physical condition score 0-3 or KPS score > 80.
the test meets the following indicators:

A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L.

B.Creatinine < 176.8 μmol/L.

C.WBC≥2.5×109/L ，LY≥0.7×109/L，LY%≥15%.

D.PT/INR < 1.7 or PT was extended by less than 4 seconds.

Exclusion Criteria:

Women who are pregnant or breastfeeding.
Patients whose tumor cell don't have positive CD19 antigen.
Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
Patients who are using steroid drugs throughout the body currently.
Patients who have received any gene therapy in the past.
Patients who are allergy to immunotherapy and related drugs.
Patients with heavy heart disease or poorly controlled high blood pressure.
Patients who received chemotherapy or radiation 4 weeks before the study began.
Patients who are participating in other clinical trials.

Sites / Locations

Hai Nan Hospital of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD19+ Lymphoma

Arm Description

This study is to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with Relapsed/Refractory B Cell Lymphoma.

Outcomes

Primary Outcome Measures

Incidence of Treatment-related Adverse Events

Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).

Secondary Outcome Measures

Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma

ORR will be assessed from the first CAR-T cell infusion to death or last follow-up

Overall survival(OS) of CD19-PD1-CART cells in Lymphoma

OS will be assessed from the first CAR-T cell infusion to death or last follow-up

Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma

PFS will be assessed from the first CAR-T cell infusion to death or last follow-up

Rate of CD19-PD1-CARTcells in peripheral blood cells

In vivo (peripheral blood) rate of CD19-PD1-CART cells were determined by means of flow cytometry.

Quantity of CD19-PD1-CART cells copies in peripheral blood cells.

In vivo (peripheral blood) quantity of CD19-PD1-CART cells copies copies were determined by means of qPCR.

Full Information

NCT ID

NCT04163302

First Posted

November 12, 2019

Last Updated

November 14, 2019

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04163302

Brief Title

Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma

Official Title

Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Unknown status

Study Start Date

July 7, 2019 (Actual)

Primary Completion Date

July 1, 2021 (Anticipated)

Study Completion Date

July 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with relapsed/refractory B Cell Lymphoma.

Detailed Description

Lymphoma is a malignant tumor originating from lymph nodes or other lymphoid tissues. It can be divided into B cells, T cells, and NK cell lymphomas depending on the origin of different lymphocytes. Among them, B cell lymphoma accounts for about 90% of lymphoma. Chimeric antigen receptor T (CART) cells is a promising treatment for lymphoma. T lymphocytes from patients are separated and engineered with CD19-CAR, to specifically recognize and eliminate CD19-positive tumor cells. At present, many CD19CART cells therapy studies are in the stage of clinical research and have achieved significant clinical effects. Although there are some CD9CART cells clinical trials, the therapeutic effect on lymphoma is significantly lower than that of acute leukemia. One of the reasons is that lymphoma has the nature of solid tumors, whichi has a certain immunosuppressive microenvironment. The clinical trials of anti-PD-1 antibody drugs against lymphoma also show good therapeutic efficacy. Therefore, the combination of anti-PD-1 or PD-L1 antibody and CD19CART is one of the ways to improve the therapeutic effect of CART cells. The investigators screened PD-1 mutants that have high bind with the PD-L1 ligand, and prepared CD19CART which secretes the mutant PD-1Fc fusion protein. Preclinical studies have shown that CD19CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect to CD19CART cells which does not express PD-1 fusion protein. The trial was conducted to explore the safety and efficacy of CD19-PD1-CART cells in Relapsed/Refractory B Cell Lymphoma.

6. Conditions and Keywords

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

Lymphoma, B-Cell

Keywords

Lymphoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, Immunotherapy, PD-1, CD19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This study was a single-center, open-label, single-arm, non-randomized clinical trial, which was divided in 3 groups by different infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CD19+ Lymphoma

Arm Type

Experimental

Arm Description

This study is to evaluate the efficacy and safety of CD19-PD1-CART cells therapy for patients with Relapsed/Refractory B Cell Lymphoma.

Intervention Type

Biological

Intervention Name(s)

CD19-PD1-CART Cell

Intervention Description

This study was a single-center, open-label, single-arm, non-randomized clinical trial, which has 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patients in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, the investigators select the safest dose and recruit more patients for CART test to explore its effectiveness.

Primary Outcome Measure Information:

Title

Incidence of Treatment-related Adverse Events

Description

Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall Remission Rate(ORR) of CD19-PD1-CART cells in Lymphoma

Description

ORR will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Overall survival(OS) of CD19-PD1-CART cells in Lymphoma

Description

OS will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Progress-free survival(PFS) of CD19-PD1-CART cells in Lymphoma

Description

PFS will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Rate of CD19-PD1-CARTcells in peripheral blood cells

Description

In vivo (peripheral blood) rate of CD19-PD1-CART cells were determined by means of flow cytometry.

Time Frame

3 years

Title

Quantity of CD19-PD1-CART cells copies in peripheral blood cells.

Description

In vivo (peripheral blood) quantity of CD19-PD1-CART cells copies copies were determined by means of qPCR.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, aged 14 to 80 years (including 14 and 80 years old). The diagnosis was Refractory/relapsed B-cell lymphoma.(Meeting 1 of the first 4 items plus item 5) A.Tumor shrinkage less than 50% or disease progression after 4 cycles of standard chemotherapy. B.Achieved CR after standard chemotherapy, but relapsed within 6 months. C.2 or more relapses after CR. D.Not suitable for HSCT, or relapse after HSCT. E.Subjects must have received adequate treatment in the past and the predicted survival is more than three months. Patient or his or her legal guardian voluntarily participates in this stuy and signs an informed consent form. Flow cytometry or immunohistochemistry showed CD19 positive in tumor cells. No serious concomitant disease and major organ function is not serious abnormal. ECOG physical condition score 0-3 or KPS score > 80. the test meets the following indicators: A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L. B.Creatinine < 176.8 μmol/L. C.WBC≥2.5×109/L ，LY≥0.7×109/L，LY%≥15%. D.PT/INR < 1.7 or PT was extended by less than 4 seconds. Exclusion Criteria: Women who are pregnant or breastfeeding. Patients whose tumor cell don't have positive CD19 antigen. Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection. Patients who are using steroid drugs throughout the body currently. Patients who have received any gene therapy in the past. Patients who are allergy to immunotherapy and related drugs. Patients with heavy heart disease or poorly controlled high blood pressure. Patients who received chemotherapy or radiation 4 weeks before the study began. Patients who are participating in other clinical trials.

Central Contact Person:

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

Quanshun Wang

Phone

15692538521

wqs63@sohu.com

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

Wenshuai Zheng

Phone

15701572628

18766179210@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Quanshun Wang

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Wengshuai Zheng

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Lixun Guan

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lu Wang

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yuanyuan Xu

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yalei Hu

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zhengyang Gu

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hai Nan Hospital of Chinese PLA General Hospital

City

Sanya

State/Province

Hainan

ZIP/Postal Code

572000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wenshuai Zheng

Phone

15701572628

18766179210@163.com

First Name & Middle Initial & Last Name & Degree

Lixun Guan

Phone

15692537637

15210758157@126.com

First Name & Middle Initial & Last Name & Degree

Quanshun Wang

First Name & Middle Initial & Last Name & Degree

Lixun Guan

First Name & Middle Initial & Last Name & Degree

Wenshuai Zheng

First Name & Middle Initial & Last Name & Degree

Zhenyang Gu

First Name & Middle Initial & Last Name & Degree

Lu Wang

First Name & Middle Initial & Last Name & Degree

Yuanyuan Xu

First Name & Middle Initial & Last Name & Degree

Yalei Hu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Safety and Efficiency Study of CD19-PD1-CART Cell in Relapsed/Refractory B Cell Lymphoma

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