Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients

Обзор

This is an early exploratory phase, single arm, non-randomized, open label, treatment study trial to determine the maximum tolerated dose of GC012F injection (CD19-BCMA CAR-T cells) in patients with refractory systemic lupus erythematosus.

Подробное описание

Systemic lupus erythematosus (SLE) is a kind of autoimmune diseases mediated by autoantibody-forming immune complexes, which involving multiple systems and organs.

Autoreactive B cells can self-activate and differentiate into plasma cells releasing large amounts of autoantibodies, while they can also present their own antigens to autoimmune T cells, thus activating T cells and promoting the release of inflammatory factors.

Traditional SLE treatment aims at long-term remission, while, CD19- BCMA CAR-T cells can theoretically completely deplete abnormal antibody-producing B cells, allowing immune rebuilding and restoring the patient's normal immune function, achieving drug-free survival, which fully reflects the application prospects of CAR-T therapy in SLE.

Вмешательства

• Препарат GC012F injection
  Each subject will receive GC012F injection (CD19-BCMA CAR-T cells) by intravenous infusion on Day 0.

Первичные конечные точки

• The proportion of subjects with DLT [Срок оценки: Within 28 days after GC012F injection infusion]
• The proportion of subjects with adverse events [Срок оценки: Within 12 weeks after GC012F injection infusion]

Вторичные конечные точки (2)

• Proportion of subjects achieving SRI-4 [Срок оценки: 4, 8, 12 and 24 weeks after GC012F injection infusion]
• Number of CAR-T cells and CAR gene copies in subjects'blood and bone marrow (if applicable) [Срок оценки: After GC012F injection infusion [day 4, 7, 10, 14 and week 4, 8, 12, 24]]

Критерии участия

Критерии включения

• 18-70 years old;
• Total score ≥ 10 on the EULAR/ACR 2019 SLE classification criteria;
• LLDAS response criteria are not achieved after administration with at least two immunosuppressants (including, but not limited to, azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, ciclosporin and iguratimod) and/or at least one approved biological agent for more than 6 months.
• SELENA-SLEDAI≥8;
• Patients with CD19+ B-cell;
• Hemoglobin≥85 g/L;
• WBC≥2.5×10\^9/L
• NEUT≥1×10\^9/L;
• BPC≥50×10\^9/L;
• AST/ALT below 2 times the upper limit of normal; Creatinine clearance ≥30 mL/min; blood bilirubin ≤2.0 mg/dl; echocardiography indicates that the ejection fraction is ≥50%;
• Adequate venous access for apheresis, and no other contraindications for leukapheresis;
• Women of childbearing age should have a negative serum or urine pregnancy test at screening and baseline. Subjects agree to take effective contraceptive measures during the trial until at least 1 year after CAR-T cells infusion.
• Agree to attend follow-up visits as required;
• Voluntary participation and informed consent signed by the patient or his/her legal/authorized representative;

Критерии исключения

• Renal disease: severe lupus nephritis (serum creatinine > 2.5 mg/dL or 221 μmol/L) within 8 weeks prior to leukapheresis, or subjects who need hemodialysis;
• CNS disease: including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident \[CVA\], encephalitis or CNS vasculitis, psychiatric patients with depression or suicidal thoughts;
• Patients with serious lesions and history of present illness of vital organs such as heart, liver, kidney and blood and endocrine system;
• Patients with immunodeficiency, uncontrolled active infections and active or recurrent peptic ulcers;
• Received immunosuppressive therapy within 1 week prior to leukapheresis;
• Patients with HIV infection; Active infection of hepatitis B virus or hepatitis C virus; Patients with syphilis infection;
• The presence or suspicion of an active fungal, bacterial, viral or other infection that cannot be controlled during screening;
• Received live vaccine treatment within 4 weeks prior to screening;
• Severe allergies or hypersensitivity;
• Contraindication to cyclophosphamide in combination with fludarabine;
• Subjects who have undergone major surgery within 2 weeks prior to signing the informed consent form, or who are scheduled to have surgery (other than local anesthetic surgery) during the trial or within 2 weeks of the infusion;
• cannula or drainage tubes other than central venous catheters;
• Pregnant or lactating women, or subjects who plan to have children within 1 year of treatment;
• Subjects with prior CD19 or BCMA-targeted therapy
• Participated in any clinical study within 3 months prior to enrollment
• Subjects with malignant tumour, except for Non-melanoma Skin Cancer with PFS>5yr; Cervical Cancer in situ; Bladder Cancer; Breast Cancer;
• Any situations that the investigator believes the patients are not suitable for the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai Jia — Шанхай

Идентификаторы

NCT: NCT05858684 · GC012F-615

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗