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

NCT07546630 | Not Yet Recruiting Early Phase 1

• 1 other identifier: VHH CAR2019-XYBYXB
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Relapsed/Refractory B-Cell Lymphoma

Keywords

Relapsed/Refractory B-Cell Lymphoma; Nanobody; CD19; CD20; CAR-T

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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.

  Within 3 months following infusion of CD19/CD20 Tandem Dual CAR-T

Other Outcomes (1)

• 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.

Study Arms (1)

This is a single arm treatment of CD19/CD20 Tandem Dual CAR-T

EXPERIMENTAL

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

Interventions

CD19/CD20 Tandem Dual CAR-T GENETIC

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.

This is a single arm treatment of CD19/CD20 Tandem Dual CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Aged 18-75 years (inclusive), male or female
• Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2
• Estimated overall survival of more than 3 months from the date of signing the informed consent form
• Hemoglobin (HGB) ≥ 70 g/L (transfusion permitted)
• 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
• The subject agrees to use contraceptive measures from the date of signing the informed consent form until 1 year after CAR-T cell infusion

You may not qualify if:

• 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

Sponsors & Collaborators

• Affiliated Hospital to Academy of Military Medical Sciences: lead

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Yamei Wu

CONTACT

+86 01066947164; rippleya@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A classic "3+3" dose escalation will be employed. The starting dose is 2×10\^6 cells/kg, followed by sequential escalated doses of 4×10\^6 cells/kg and 6×10\^6 cells/kg.If no dose-limiting toxicity (DLT) is observed in 3 subjects at a given dose cohort, the study may proceed to the next higher dose level. Dose escalation will be discontinued if DLT occurs in 2 or more out of 3 subjects. If 1 DLT event occurs in the initial 3 subjects, another 3 subjects will be enrolled at the same dose. Escalation may continue if no DLT occurs in the supplementary 3 subjects. Dose escalation shall not proceed if DLT occurs in any of the additional subjects, or if a total of 2 or more DLT cases occur among 6 subjects in the same cohort.DLT refers to reasonably treatment-related toxic reactions within the DLT assessment window (Day 1 to Day 28 after CAR-T infusion), and toxicity grading shall comply with CTCAE 5.0.

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 23, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share