CD19/ CD22 Bispecific CAR-T Cell Therapy for Relapsed/ Refractory Large B-cell Lymphoma

CD19/ CD22 Bispecific CAR-T Cell Therapy for Relapsed/ Refractory Large B-cell Lymphoma: A Prospective, Single-Arm, Single-Center, Phase 2 Trial

CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, the investigators supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B- NHL. In this prospective phase 2 clinical trial, the investigators aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory Large B cell lymphoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Large B-Cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: CD19/CD22 bispecific CAR-T cells

Detailed Description

Large B cell lymphoma (LBCL) is the most common aggressive subtype of non-Hodgkin lymphoma (NHL) in adults. While approximately 60% of patients can be cured with first-line therapy, a subset of patients experiences relapse or refractory disease (R/R). The prognosis for R/R LBCL patients is poor, with limited efficacy from traditional treatments such as autologous stem cell transplantation (ASCT) and novel targeted agents. Chimeric antigen receptor-T (CAR-T) cell therapy involves genetically engineering T cells to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enabling precise elimination of tumor cells. CD19 is the most commonly targeted antigen in B-cell malignancies, however, antigen escape following CD19 CAR-T therapy can lead to disease relapse in some patients. Studies indicate that CD22 is widely expressed in B-cell malignancies and exhibits incomplete overlap with CD19 expression, suggesting that dual-target CAR-T therapy may more comprehensively eradicate tumor cells. Therefore, dual-target CAR-T therapy, particularly strategies targeting both CD19 and CD22, has emerged as a promising approach to overcome antigen escape and enhance therapeutic outcomes. In this prospective study, the investigators aimed to evaluate the efficacy and safety of CD19/CD22 bispecific CAR-T cell (CAR2219) therapy in patients with R/R LBCL.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Tongren Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 14 years to 85 years, expected survival > 3 months;
• CD19 positive with or without CD22 positive Large B-cell lymphoma;
• relapsed or refractory disease;
• ECOG-PS score=0-2;
• Having at least one measurable lesion;
• Cardiac function: 1-2 levels;
• Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN;
• kidney: Cr≤1.25ULN;
• bone marrow: WBC ≥ 3.0×10e9/L, Hb ≥80 g/L, PLT ≥ 50×10e9/L;
• No serious allergic constitution;
• No other serious diseases that conflicts with the clinical program;
• No other cancer history;
• No serious mental disorder;
• Informed consent is signed by a subject or his lineal relation.

Exclusion Criteria:

• Pregnant or lactating women (female participants of reproductive potential must have a negative serum or urine pregnancy test);
• Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
• Active hepatitis B or hepatitis C infection;
• With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
• Participate in other clinical research in the past 4 weeks;
• Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results.

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/CD22 CAR-T group; Patients would receive autologous CAR-T cell therapy targeting both CD19 and CD22. The dosage for CD19/CD22 bispecific CAR-T cells was 2×10e6/kg.	Drug: CD19/CD22 bispecific CAR-T cells; CD19/CD22-bispecific CAR-T cells were infused at the dosage of 2×10e6/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
best overall response rate (ORR) as of 3 months post-CAR-T cells infusion	Overall response rate means sum of complete response rate and partial response rate	From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS was defined from the date of CAR-T infusion to the date fo confirmed disease progression or death of any reason	From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
overall survival (OS)	OS was defined from the date of CAR-T infusion to the date fo death	From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
Best Complete Response rate (CR) as of 3 months post-CAR-T cells infusion	CR was defined as complete response evaluated using PET-CT scan	From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	measured using CTCAE version 5.0	From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital
• Investigators: Principal Investigator: Liang Wang, M.D., Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): April 18, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 18, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; bispecific; Large B-cell Lymphoma; CD19/CD22
• Other Study ID Numbers: TRhos-CART-02; 2025ZD0544300 (Other Grant/Funding Number: Noncommunicable Chronic Diseases-National Science and Technology Major Project)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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