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

Sponsor

The First Affiliated Hospital of Soochow University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04539444

Collaborator

Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd (Industry)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Non Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma	Biological: CD19/22 CART Drug: Tislelizumab	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Feb 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD19/22 CART cells combined with PD-1 inhibitors Patients will receive PD-1 inhibitor on the first day after CART cell infusion	Biological: CD19/22 CART CD19/22 CART cells are administrated in a 3-day split-dose regimen at dose of 0.5- 2×10107 CART cells per kilogram of body weight. Drug: Tislelizumab* Patients will receive Tislelizumab 200mg/dose every 3 weeks. Other Names: PD-1 inhibitor

Arm

Intervention/Treatment

Experimental: CD19/22 CART cells combined with PD-1 inhibitors

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

Biological: CD19/22 CART

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.

Drug: Tislelizumab

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

Other Names:

PD-1 inhibitor

Outcome Measures

Primary Outcome Measures

Overall response rate (ORR) [1 year]
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) [1 year]
PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.

Secondary Outcome Measures

Complete relapse rate(CR) [1 year]
Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor.
Duration of overall response (DOR) [1 year]
Duration of overall response will be assessed from the first CAR-T cell infusion to progression,death or last follow-up.
Overall survival(OS) [1 year]
OS will be assessed from the first CART cell infusion to death or last follow-up.
Incidence of treatment-related adverse events [1 year]
The incidence rate of adverse events from the first day of preconditioning chemotherapy to 1 year after CART cells infusion

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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)

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