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

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

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.

Study Overview

• Status: Completed
• Conditions: Refractory Non-Hodgkin Lymphoma; Relapsed Non Hodgkin Lymphoma
• Intervention / Treatment: Biological: CD19/22 CART; Drug: Tislelizumab

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. Age ≥ 18 years
3. The Eastern Cooperative Oncoloy Group (ECOG) physical condition score ≤ 2 points

4. 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%

5. Results of pregnant test should be negative, and agree to conception control during treatment and 1 year after CAR-T infusion
6. Expected survival exceeds 3 months
7. Written informed consent could be acquired

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year
Progression-free survival(PFS)	PFS will be assessed from the first CART cell infusion to progression,death or last follow-up.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete relapse rate(CR)	Number of patients who achieved complete response after treatment by CD19/22 CART combined with PD-1 inhibitor.	1 year
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.	1 year
Overall survival(OS)	OS will be assessed from the first CART cell infusion to death or last follow-up.	1 year
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	1 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
• Investigators: Study Chair: Depei Wu, M.D., The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): September 30, 2022
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: August 31, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: PD-1 inhibitor; Chimeric antigen receptor T cells; Relapsed or refractory B cells non-Hodgkin's lymphoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, Non-Hodgkin; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors; tislelizumab
• Other Study ID Numbers: CCPD-1 in lymphoma

Drug and device information, study documents

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