UCAR T-cell Therapy Targeting CD19/ BCMA in Patients With Relapse/ Refractory Autoimmune Diseases

Official title

A Clinical Study Evaluating the Safety and Preliminary Efficacy of Universal Allogeneic CAR T-cell Therapy Targeting CD19 and BCMA in Patients With Relapse/Refractory Autoimmune Diseases

Overview

This is an investigator-initiated trial to evaluate the safety and efficacy of universal allogeneic anti-CD19/BCMA CAR T-cells in With Relapse/Refractory Autoimmune Diseases.

Detailed description

This is an investigator-initiated trial to evaluate the safety and efficacy ofuniversal allogeneic anti-CD19/BCMA CAR T-cells in Patients With Relapse/Refractory Autoimmune Diseases.

Study intervention consists of a single infusion of universal allogeneic CART-cells administered intravenously after a lymphodepleting therapy regimen consisting of fludarabine and cyclophosphamide.

Interventions

• Biological universal allogeneic anti-CD19/BCMA CAR T-cells
  A single injection of UCAR T-cells, referred to as universal allogeneic anti-CD19/BCMA CAR T-cells

Primary outcome measures

• The number and severity of dose-limiting toxicity (DLT) events [Time frame: Within 28 Days After UCAR T-cell Infusion]
• The total number, incidence, and severity of AEs [Time frame: Up to 90 days After UCAR T-cell Infusion]

Secondary outcome measures (9)

• AIHA：Rates of CR, CRi, PR, ORR [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• SLE：SLE Response Index 4 (SRI-4) [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• SLE: Change in the Systemic Lupus Erythematosus Disease Activity Index(SLEDAI) from baseline [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• SSc：Change in the modified Rodnan Skin Score (mRSS) from baseline [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• IIM：The ACR-EULAR Myositis Response Criteria [Total Improvement Score (TIS)] [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• AAV: Change in disease activity as measured by Birmingham Vasculitis Activity Score (BVAS) [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• IgG4-RD:IgG4-Related Disease Responder Index (IgG4-RD RI) [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• MG:Changes of Myasthenia Gravis Activities of Daily Living (MG-ADL) Score [Time frame: Up to 24 Months After UCAR T-cell Infusion]
• MG:Quantitative Myasthenia Gravis Score (QMG) [Time frame: Up to 24 Months After UCAR T-cell Infusion]

Eligibility criteria

Inclusion criteria

• 1.Age ≥ 18 years old (inclusive), regardless of gender.
• 2.Positive expression of CD19 on peripheral blood B cells confirmed by flow cytometry.
• 3.Functional requirements for major organs are as follows:

• Bone marrow function must meet: A. Neutrophil count ≥ 0.5×10 \^ 9/L (no colony-stimulating factor treatment within 2 weeks before examination); B. Hemoglobin ≥ 60g/L; C. Platelets ≥ 30 × 10 \^ 9/L.
• Liver function: Alanine aminotransferase (ALT) ≤ 3×ULN (excluding ALT elevation due to inflammatory myopathy), aspartate aminotransferase (AST)≤3×Upper limit of normal (ULN) (excluding AST elevation due to inflammatory myopathy), TBIL≤1.5×ULN (or ≤ 3.0×ULN for subjects with Gilbert syndrome);
• Renal function: creatinine clearance rate (CrCl) ≥ 30ml/minute (calculated by Cockcroft/Gault formula, acute CrCl decrease due to the target disease is excluded; LN is exluded);
• 4.ECOG score 0-1.
• 5.Female subjects of childbearing potential and male subjects with partners of childbearing potential must use medically approved contraception or abstinence during the study treatment period and for at least 6 months after the end of the study treatment; Female subjects of childbearing potential must have a negative Human chorionic gonadotropin (HCG) test within 7 days before study enrollment and not be lactating.
• 6.Willing to participate in this clinical study, sign an informed consent form, have good compliance, and cooperate with follow-up.
• 7.Subjects with relapsed or refractory autoimmune diseases, Including relapsed or refractory Autoimmune Hemolytic Anemia, relapsed or refractory Systemic Lupus Erythematosus, relapsed or refractory or Progressive Systemic Sclerosis, relapsed or refractory or Progressive Inflammatory Myopathy, relapsed or refractory ANCA-Associated Vasculitis, relapsed or refractory Immunoglobulin-G4 related disease and relapsed or refractory Myasthenia Gravis.

Exclusion criteria

• 1.Subjects with a history of severe drug allergies or allergic constitutions;
• 2\. Presence or suspicion of uncontrolled or treatment-required fungal, bacterial, viral, or other infections;
• 3\. Subjects with insufficient cardiac function;
• 4\. Subjects with congenital immunoglobulin deficiencies;
• 5\. Subjects with a history of malignant tumors within the past five years, except for the following conditions: non-melanoma skin cancer, stage I tumors with a low recurrence probability after complete resection, clinically localized prostate cancer after treatment, cervical carcinoma in situ confirmed by biopsy or squamous intraepithelial lesion shown by smear, and stable papillary thyroid carcinoma or follicular thyroid carcinoma.
• 6\. Subjects who are positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood HBV DNA >ULN; subjects positive for hepatitis C virus (HCV) antibody and peripheral blood HCV RNA; individuals positive for human immunodeficiency virus (HIV) antibody; individuals positive for syphilis testing;
• 7\. Subjects with mental illness and severe cognitive dysfunction;
• 8\. Pregnant women or women planning to conceive;
• 9.Subjects whom the investigator believes have other reasons that make them unsuitable for inclusion in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Changzhou No.2 People's Hospital — Changzhou

Identifiers

NCT: NCT06978738 · QH-CE-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗