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A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma

Primary Purpose

Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

CD19/22 CART

Tislelizumab

About this trial

This is an interventional treatment trial for Relapsed Non Hodgkin Lymphoma focused on measuring Chimeric antigen receptor T cells, Relapsed or refractory B cells non-Hodgkin's lymphoma, PD-1 inhibitor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

R/R B-NHL with measurable (≧1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions):
A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen
Age ≥ 18 years
The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points
The main organ functions need to meet the following conditions:
A.Left ventricular ejection fraction ≥50% B.Creatinine ≤132umol/l or creatinine clearance ≥60 ml/min C.ALT and AST≤2 upper limitation of normal D.SpO2 > 90%
Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion
Expected survival exceeds 3 months
Written informed consent could be acquired

Exclusion Criteria:

Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years
Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection
Active hepatitis B or hepatitis C infection
HIV infection
Severe acute or chronic graft-versus-host disease (GVHD)
Participated in any other drug research clinical trials within 30 days before enrollment
Prior CART cells therapy within 3 months before enrollment
Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment
Have contraindications to the PD-1 inhibitors
Uncontrolled other tumor
Women in pregnancy,lactation or planning to become pregnant
The researcher considers inappropriate to participate in this research

Sites / Locations

The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD19/22 CART cells combined with PD-1 inhibitors

Arm Description

Patients will receive PD-1 inhibitor on the first day after CART cell infusion

Outcomes

Primary Outcome Measures

Overall response rate (ORR)

Number of patients who achieved response (complete response and partial response ) after treatment of CD19/22 CART combined with PD-1 inhibitor. Response will be assessed using the Lugano criteria.

Progression-free survival(PFS)

PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.

Secondary Outcome Measures

Complete relapse rate(CR)

Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor.

Duration of overall response (DOR)

Duration of overall response will be assessed from the first CAR-T cell infusion to progression,death or last follow-up.

Overall survival(OS)

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

Incidence of treatment-related adverse events

The incidence rate of adverse events from the first day of preconditioning chemotherapy to 1 year after CART cells infusion

Full Information

NCT ID

NCT04539444

First Posted

August 31, 2020

Last Updated

July 30, 2021

Sponsor

The First Affiliated Hospital of Soochow University

Collaborators

Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

1. Study Identification

Unique Protocol Identification Number

NCT04539444

Brief Title

A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma

Official Title

A Study Evaluated Efficacy and Safety of CD19/22 Chimeric Antigen Receptor T Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Unknown status

Study Start Date

August 1, 2020 (Actual)

Primary Completion Date

February 1, 2022 (Anticipated)

Study Completion Date

February 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital of Soochow University

Collaborators

Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

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 CD19/22 CART cells combined with PD-1 Inhibitor in relapsed/refractory B Cell Lymphoma.

Detailed Description

Though response rates have greatly improved with the development of Chimeric antigen receptor T cells (CART) therapy in refractory/relapsed B cell non-Hodgkin's lymphoma (R/R B-NHL), the response can't usually last long and relapse occurs in a large proportion of patients who receive CART cells infusion. The main reasons of relapse might be tumor antigen loss and a lack of CART cell persistence. Currently, preclinical studies have shown that there is a synergistic effect between CAR-T cell therapy and anti-PD1 pathway, and it did have efficacy in clinic. In parallel, the combined use of CART-19 and CART-22 cells has a better potential to reduce antigen escape and increase anti-tumor activity. Therefore, the combination of CD19/22 CART and PD-1 inhibitor is one of the ways to improve the therapeutic effect of CART cells. This study was conducted to explore the efficacy and safety of CD19/22 CART cells in R/R B-NHL.

6. Conditions and Keywords

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

Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

Keywords

Chimeric antigen receptor T cells, Relapsed or refractory B cells non-Hodgkin's lymphoma, PD-1 inhibitor

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CD19/22 CART cells combined with PD-1 inhibitors

Arm Type

Experimental

Arm Description

Patients will receive PD-1 inhibitor on the first day after CART cell infusion

Intervention Type

Biological

Intervention Name(s)

CD19/22 CART

Intervention Description

CD19/22 CART cells are administrated in a 3-day split-dose regimen at dose of 0.5- 2×10*107 CART cells per kilogram of body weight.

Intervention Type

Drug

Intervention Name(s)

Tislelizumab

Other Intervention Name(s)

PD-1 inhibitor

Intervention Description

Patients will receive Tislelizumab 200mg/dose every 3 weeks.

Primary Outcome Measure Information:

Title

Overall response rate (ORR)

Description

Number of patients who achieved response (complete response and partial response ) after treatment of CD19/22 CART combined with PD-1 inhibitor. Response will be assessed using the Lugano criteria.

Time Frame

1 year

Title

Progression-free survival(PFS)

Description

PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Complete relapse rate(CR)

Description

Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor.

Time Frame

1 year

Title

Duration of overall response (DOR)

Description

Duration of overall response will be assessed from the first CAR-T cell infusion to progression,death or last follow-up.

Time Frame

1 year

Title

Overall survival(OS)

Description

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

Time Frame

1 year

Title

Incidence of treatment-related adverse events

Description

The incidence rate of adverse events from the first day of preconditioning chemotherapy to 1 year after CART cells infusion

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: R/R B-NHL with measurable (≧1.5cm) lesions confirmed by pathological immunohistochemistry or flow cytometry ( meeting any of the following conditions): A.The lesion shrinkage <50% or disease progression after 4 courses of standard first-line treatment or 2 courses of two-line treatment (primary refractory disease) B. Progress disease as the best response after hematopoietic stem cell transplantation C.Progress disease or stable disease as the best response to most recent therapy regimen Age ≥ 18 years The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points The main organ functions need to meet the following conditions: A.Left ventricular ejection fraction ≥50% B.Creatinine ≤132umol/l or creatinine clearance ≥60 ml/min C.ALT and AST≤2 upper limitation of normal D.SpO2 > 90% Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion Expected survival exceeds 3 months Written informed consent could be acquired Exclusion Criteria: Immunosuppressant medications or steroids was used within 2 weeks before cell collection, or need to use steroids or immunosuppressant medications more than two years Uncontrolled bacteria, fungi, viruses, mycoplasma or other types of infection Active hepatitis B or hepatitis C infection HIV infection Severe acute or chronic graft-versus-host disease (GVHD) Participated in any other drug research clinical trials within 30 days before enrollment Prior CART cells therapy within 3 months before enrollment Prior allogeneic hematopoietic stem cell transplantation within 6 months before enrollment Have contraindications to the PD-1 inhibitors Uncontrolled other tumor Women in pregnancy,lactation or planning to become pregnant The researcher considers inappropriate to participate in this research

Central Contact Person:

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

Caixia Li, M.D.

Phone

+86 512 67781856

licaixia@suda.edu.cn

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

Jia Chen, M.D.

Phone

+86 512 67781856

chenjiasuzhou@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Depei Wu, M.D.

Organizational Affiliation

The First Affiliated Hospital of Soochow University

Official's Role

Study Chair

Facility Information:

Facility Name

The First Affiliated Hospital of Soochow University

City

Suzhou

State/Province

Jiangsu

ZIP/Postal Code

215000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Caixia Li

12. IPD Sharing Statement

Learn more about this trial

A Study of CD19/22 CART Cells Combined With PD-1 Inhibitor in Relapsed/Refractory B-cell Lymphoma

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