Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell Therapy of Relapsed/Refractory B-Cell Lymphoma

Clinical Study on the Safety and Efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell Therapy for Relapsed/Refractory B-Cell Lymphoma

This is a single arm study to evaluate the safety and efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for Relapsed/Refractory B-Cell Lymphoma

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed/Refractory B-Cell Lymphoma
• Intervention / Treatment: Genetic: CD19/CD20 Tandem Dual CAR-T

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Yamei Wu; Phone Number: +86 01066947164; Email: rippleya@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The subject has voluntarily signed the informed consent form with full consent, and is willing and able to comply with the scheduled visits, study treatments, laboratory tests, and other trial procedures

2. Patients with relapsed/refractory B-cell lymphoma confirmed by cytology or histology according to the WHO 2022 Classification:

   • Lymphoma cells confirmed to express CD19 and/or CD20 antigen by immunophenotyping or histopathological immunohistochemistry
   • B-cell lymphomas include: aggressive B-cell lymphomas (LBCL, BL, MCL) and indolent B-cell lymphomas (CLL/SLL, FL, MZL, LPL, HCL)
   • Relapsed/refractory B-cell lymphoma: For patients with aggressive lymphoma, disease stable for ≤12 months or disease progression after achieving best response following at least first- and second-line pharmacotherapy; or disease progression or relapse within ≤12 months after autologous stem cell transplantation. For patients with indolent lymphoma, disease progression, relapse or transformation following at least three lines of prior therapy
3. Aged 18-75 years (inclusive), male or female
4. Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
5. Estimated overall survival of more than 3 months from the date of signing the informed consent form
6. Hemoglobin (HGB) ≥ 70 g/L (transfusion permitted)

7. Adequate hepatic, renal and cardiopulmonary function meeting the following criteria:

   • Creatinine ≤ 1.5 × ULN;
   • Left ventricular ejection fraction (LVEF) ≥ 50%;
   • Blood oxygen saturation > 90%;
   • Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN
8. The subject agrees to use contraceptive measures from the date of signing the informed consent form until 1 year after CAR-T cell infusion

Exclusion Criteria:

• Severe cardiac insufficiency with left ventricular ejection fraction < 50%
• History of severe pulmonary function-impairing diseases
• Concomitant other advanced malignant neoplasms
• Concomitant severe infection that cannot be effectively controlled
• Concomitant severe autoimmune diseases or congenital immunodeficiency disorders
• Active hepatitis (hepatitis B virus deoxyribonucleic acid [HBV-DNA] or hepatitis C virus ribonucleic acid [HCV-RNA] test result above the lower limit of detection)
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection
• History of severe allergy to biological products (including antibiotics)
• Patients with allogeneic hematopoietic stem cell transplantation who still have acute graft-versus-host disease (GVHD) after one month of discontinuation of immunosuppressive agents

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: This is a single arm treatment of CD19/CD20 Tandem Dual CAR-T; Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy. Investigational product: CD19/CD20 Tandem Dual CAR-T. Route of administration: Intravenous injection. Lymphodepleting chemotherapy regimen: Acombination of fludarabine and cyclophosphamide will be administered prior to the infusion of CD19/CD20 Tandem Dual CAR-T.	Genetic: CD19/CD20 Tandem Dual CAR-T; Each subject will be infused with single dose of CD19/CD20 Tandem Dual CAR-T. A classic "3+3" dose escalation will be employed. The low dose is 2×10^6 / kg, the medium dose is 4×10^6 /kg, and the high dose is 6×10^6 /kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
According to the incidence of treatment-related adverse events (AEs) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma.	Incidence of treatment-related adverse events (AEs) Description: Number and severity of adverse events graded according to CTCAE v5.0, including cytokine release syndrome (CRS) graded by ASTCT criteria and immune effector cell-associated neurotoxicity syndrome (ICANS) graded by ASBMT criteria	up to 3 years
According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safety of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma.		MTD will be determined based on DLTs observed during the first 28 days of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
According to the objective response rate (ORR) to evaluate the efficacy of Nanobody-Based CD19/CD20 Tandem Dual CAR-T-cell therapy for CD20/CD19 positive relapsed/refractory B-Cell lymphoma.	Overall Response Rate (ORR) Description:For B-cell lymphoma, ORR is defined according to the Lugano Classification for Lymphoma Response Assessment. ORR represents the proportion of patients achieving complete response (CR) or partial response (PR).	Within 3 months following infusion of CD19/CD20 Tandem Dual CAR-T

Other Outcome Measures

Outcome Measure	Time Frame
According to the pharmacokinetics (number of CAR-T cells in peripheral blood was measured to evaluate the persistence of CAR-T cells) to explore the kinetics and clonal evolution of CD19/CD20 Tandem Dual CAR-T.	Up to 12 months after CAR-T treatment.

Collaborators and Investigators

• Sponsor: Affiliated Hospital to Academy of Military Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T; CD19; CD20; Nanobody; Relapsed/Refractory B-Cell Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: VHH CAR2019-XYBYXB

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