Exploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease

ConditionsIgG4 Related Disease B-cell Mediated Autoimmune Disorders

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorChinese PLA General Hospital

About this trial

The goal of this clinical trial is to test the safety and potential benefit of a new immune cell therapy called anti-BCMA-CD19 CAR-T cells in adults (18-75 years) with IgG4-related disease (IgG4-RD) that has come back or not improved after standard treatments such as glucocorticoids or rituximab.

The main questions this study aims to answer are:

* What medical problems (side effects) occur after receiving anti-BCMA-CD19 CAR-T cell therapy? * Does anti-BCMA-CD19 CAR-T cell therapy improve IgG4-RD disease activity scores at 12 weeks and 26 weeks?

Participants will:

* Have their own blood immune cells collected by a procedure called leukapheresis * Receive short-term chemotherapy to prepare the immune system * Receive one intravenous infusion of anti-BCMA-CD19 CAR-T cells * Return for regular clinic visits over 26 weeks for safety checks, blood tests, and imaging * May be followed for up to one year in total

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged 18 to 75 years, inclusive, regardless of sex.

Meet the 2019 ACR/EULAR classification criteria for IgG4-related disease.

Involvement of two or more important systems/sites (including but not limited to the pancreas, bile ducts, kidneys and dura mater).

Relapsed or refractory IgG4-RD: The disease either remains active after 3 months of glucocorticoid and/or rituximab therapy or relapses within 6 months post-treatment.

Disqualifiers

History of severe drug allergy or allergic constitution.

Current or suspected uncontrollable or treatment-requiring fungal, bacterial, viral or other infections.

Central nervous system disease (excluding disease-related epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis or central nervous system vasculitis).

Cardiac insufficiency that precludes participation.

Trial design

Design model

Single group

Treatments tested in this trial

Anti-BCMA-CD19 CAR-T cells
Biological/Vaccine
Anti-BCMA-CD19 CAR-T cell injection is an autologous, dual-target chimeric antigen receptor T-cell therapy designed to target CD19 and BCMA antigens. Peripheral blood mononuclear cells (PBMCs) are collected from each participant and modified ex vivo using lentiviral transduction to express the CAR construct. Lymphodepletion with cyclophosphamide (250 mg/m\^2/day, IV) and fludarabine (30 mg/m\^2/day, IV) is administered for 3 days (Day -5 to Day -3). The doses of fludarabine and cyclophosphamide may be adjusted based on the patient's clinical condition. CAR-T cells are infused intravenously on Day 0 at one of three dose levels (1x10\^6, 2x10\^6, or 3x10\^6 CAR+ T cells/kg, ±20%). This product is being investigated in patients with relapsed or refractory IgG4-related disease (IgG4-RD) to assess safety and preliminary efficacy.

Treatment groups

9 Participants

are divided into 1 treatment group

Group A: Anti-BCMA-CD19 CAR-T cellsExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Safety - Incidence of Dose-Limiting Toxicity (DLT) and Adverse Events Related to CAR-T Cells

Any grade ≥3 toxicity related to CAR-T cells within 28 days post-infusion is considered a DLT, except: * Grade 3 CRS resolving to ≤ grade 2 within 3 days; * Grade 3/4 TLS \<7 days; * Hematologic: grade 3 neutropenia/anemia/thrombocytopenia at any time or grade 4 \<14 days (\<21 days for thrombocytopenia); other cytopenias excluded; * Non-hematologic: fever (incl. febrile neutropenia), grade 3 diarrhea \<7 days, grade 3 nausea/vomiting \<7 days, grade 3 fatigue \<7 days; * Grade 3/4 elevations in liver enzymes, bilirubin, creatinine, or BUN \<7 days; * Asymptomatic lipase elevation without pancreatitis; * Asymptomatic grade 3 non-hematologic lab abnormality reversible \<7 days (to baseline or ≤ grade 2). Safety monitoring includes AEs, SAEs, AESIs, CRS, and ICANS, with grading and frequency recorded.

Time frame

Baseline to Week 26

Efficacy - Changes in IgG4-RD RI

IgG4-RD Responder Index is a validated score used to assess disease activity

Time frame

Baseline, Week 12 and Week 26

Secondary outcomes

PK: Cmax of CAR-T Cells

Peak CAR transgene copies in peripheral blood

Time frame

Baseline to Week 26

PK: Tmax of CAR-T Cells

Time to peak CAR transgene level

Time frame

Baseline to Week 26

PK: AUC0-28d of CAR-T Cells

Area under the curve of CAR transgene copies over 28 days

Time frame

Baseline, Week 4

PK: AUC0-90d of CAR-T Cells

Area under the curve of CAR transgene copies over 90 days

Time frame

Baseline, W12

Other outcomes

Peripheral Blood Immune Cell Subsets

Quantification and phenotyping of T, B, NK, monocyte/macrophage subsets

Time frame

Baseline and Week 26

B-cell Subpopulations in Lesion Tissue

Flow cytometry and histology of tissue-derived B cells

Time frame

Baseline and Week 26

Plasma Cytokine and Chemokine Levels

Multiplex assays of plasma cytokines and chemokines

Time frame

Baseline and Week 26

Immune Cell Functional Status

Proliferation, activation, and exhaustion marker expression (MFI)

Time frame

Baseline and Week 26

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Chinese PLA General Hospital

Lead sponsor

Xuzhou Medical University

Collaborator

Source ClinicalTrials.gov

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