A Dose Escalating Study of CD19/CD22/BCMA CAR-T Therapy in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

A Dose Escalating Study of CD19/CD22/BCMA Three Targets Autologous Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous chimeric antigen receptor T (CAR-T) cells targeting CD19/CD22/BCMA in patients with relapsed or refractory B cell non-Hodgkin lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma, B-cell
• Intervention / Treatment: Biological: CD19/CD20/BCMA CAR T cells

Detailed Description

This is a single arm, open-label, dose escalation investigator initiated (IIT) study, the primary objective is to evaluate the safety and tolerability of CD19/CD22/BCMA CAR-T therapy in patients with B cell non-Hodgkin lymphoma, and determine the maximum tolerated dose (MTD). For the secondary objectives, pharmacokinetics(PK), survival of CAR-T cells in vivo, pharmacodynamics (PD) and efficacy in R/R B cell NHL will be evaluated.

This study flow comprises of a screening phase( ≤28 days prior to apheresis), apheresis phase (occur upon enrollment, ≤10 days prior to infusion), lymphodepletion phase (from Day -5 to Day -3) ,infusion of CD19/CD22/BCMA CAR-T cells on Day0, DLT assessments phase from Day1 to Day 28 and post-treatment follow-up phase (Day 29 and up to end of the study).

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

Contacts and Locations

• Study Contact: Name: Jinxing Lou; Phone Number: 021-67091399; Email: loujx@shcell.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201800
      • Recruiting
      • Mengchao Cancer Hospital
      • Contact: Jinxing Lou; Phone Number: 18911335396; Email: loujx@shcell.com
      • Principal Investigator: Jinxing Lou

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma , especially

  • Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS),
  • Primary Mediastinal Large B Cell Lymphoma (PMBCL)
  • Transformation Follicular Lymphoma (TFL)
  • High grade B-cell lymphoma(HGBCL)
  • High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement

• Refractory diseases are defined as one of the following

  • No response to last line of therapy: i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to most recent therapy regimen
  • Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT: i. Disease progression (PD) or relapsed ≤12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy

• Individuals must have received adequate prior therapy including at a minimum:

  • anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
  • an anthracycline containing chemotherapy regimen
• Immunohistochemical staining shows at least two of B cell surface receptor antigen CD19,CD20, BCMA are positive(including weak, medium and strong positive)
• At least one measurable lesion during the screening based on the recommendation for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma.
• Life expectancy ≥ 12 weeks
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1

• Adequate renal, hepatic, pulmonary and cardiac function defined as:

  • Renal function: Serum creatinine ≤ 1.5 upper limit of normal(ULN), or eGFR ≥ 60 mL/min/1.73m2 [eGFR(estimated glomerular filtration rate)=186×age^-0.203×SCr^-1.154（mg/dl）,female×0.742]
  • Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 ULN and ii: total bilirubin ≤ 2 ULN, except in individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).iii: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Pulmonary: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air
  • Cardiac: left ventricular ejection fraction (LVEF) ≥50% determined by echocardiogram(ECG) or multigated acquisition scan (MUGA)

• Adequate bone marrow function, define as:

  • absolute neutrophil count (ANC) ≥1 ×10^9/L
  • absolute lymphocyte count (ALC)≥ 0.5 ×10^9/L
  • Platelets ≥50 ×109/L；
  • Hemoglobulin ≥80 g/L; patients with bone marrow involvement can be enrolled if globulin>60 g/L
• Female of child-bearing age and male participants must agree to use effective contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain reaction) test.

Key Exclusion Criteria:

• Individuals who have antiCD45 or antiCD3 therapy
• Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of primary or secondary CNS (central nervous system) lymphoma, cerebrospinal fluid malignant cells or brain metastases
• Presence or history of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
• History of allogeneic stem cell transplantation

• Any of the following situations:

  • HBsAg/ HBeAg positive; HBeAb/HBcAb positive and HBV(hepatitis B virus) DNA copies above the lower test limit;

• HCV(hepatitis C virus) RNA positive
• HIV(human immunodeficiency virus) positive or treponema pallidum positive
• Presence of active or life-threatening fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
• Individuals presence of unstable angina or myocardial infarction within 6 months of screening, or other severe/uncontrolled diseases during the screening (eg. Unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
• Presence of uncontrolled arrhythmia with treatment
• Pregnancy or breastfeeding women

Other protocol defined inclusion/exclusion criteria may apply.

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/CD20/BCMA CAR T therapy; The safety and tolerability of BZE2204 will be assessed in a "1+1+1+3" and "3+3" dose escalation approach in different B-cell non-hodgkin lymphoma	Biological: CD19/CD20/BCMA CAR T cells; Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of CD19/CD20/BCMA CAR T cells. Cyclophosphamide and fludarabine will be given from day-5 to day-3 before the infusion for lymphodepletion. On day0 subjects will receive one dose treatment with CD19/CD20/BCMA CAR T cells by intravenous (IV) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity(DLT)	Safety	Day0-Day28
Maximum tolerated dose (MTD)	Tolerability	Day0-Day28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration(Cmax)	Pharmacokinetics (PK)	Day0-Day28，Day0-undetectable for CAR positive T cells
Maximum Plasma Concentration Time (Tmax)	Pharmacokinetics (PK)	Day0-Day28，Day0-undetectable for CAR positive T cells
Area Under Curve (AUC)	Pharmacokinetics(PK)	Day0-Day28，Day0-undetectable for CAR positive T cells
CAR positive T cells	Pharmacokinetics(PK)	Day0-Day28，Day0-undetectable for CAR positive T cells
Cytokines ( IL(interleukin)-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN(interferon)-γ, TNF(tumor necrosis factor)-α and MCP( monocyte chemoattractant protein)-1)	Pharmacodynamics (PD)	Day0-Day28
Overall survival (OS)	Clinical response assessed by Lugano Response Criteria for non-Hodgkin Lymphoma	Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24
Progression-free survival (PFS)	Clinical response assessed by Lugano Response Criteria for non-Hodgkin Lymphoma	Day28,Month2,Month3,Month6,Month9,Month12,Month18,Month24

Collaborators and Investigators

• Sponsor: Shanghai Cell Therapy Group Co.,Ltd
• Investigators: Principal Investigator: Jinxing Lou, Shanghai Mengchao Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; CD19; BCMA; CD22; B cell non-hodgkin lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: BZE2204-A-01

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
• product manufactured in and exported from the U.S.: No