NCT07544225尚未招募1 期
Study Investigating the Safety of Anti-CD19 CAR-T Cells Therapy Produced at Gustave Roussy for Adults With Severe and Refractory Systemic Autoimmune Rheumatic Diseases
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Unacceptable toxicities over a period of 4 weeks after the single CAR-T cell infusion
研究概览
简要总结
This is an open-label, single-dose, prospective, monocenter, Phase I interventional study (not first-in-human) to assess the safety, tolerability, and preliminary efficacy of autologous anti-CD19 CAR-T cells as an advanced therapy medicinal product in adult patients; with severe and refractory systemic autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's disease (SjD), systemic sclerosis (SSc) and idiopathic inflammatory myositis (IIM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 and ≤ 75 years of age at the time of inclusion visit.
- •ECOG Performance status 0 to
- •Signed informed consent (or legal representative) must be obtained from the patient prior to participation in the study.
- •Patients must have valid health insurance coverage in the country where the study is conducted.
- •A diagnosis of treatment-refractory systemic autoimmune rheumatic disease (rheumatoid arthritis (RA), severe lupus erythematosus (SLE), Sjogren's disease (SjD), Systemic sclerosis (SSc) or idiopathic inflammatory myositis (IIM)) with a severe and progressive disease according to respective criteria below.
- •Eligible patients must have failed at least two lines of conventional or biologic immunosuppressive therapies
- •Calculated creatinine clearance (calculated using CKD-EPI 2021 Formula) > 30 mL/min
- •Women of childbearing potential must agree to use highly effective contraception or practice true sexual abstinence for at least 1 month before study start and until 12 months after CAR-T cells infusion. (see section 7.7 " Pregnancy and contraception ").
- •Male patients must agree to practice true sexual abstinence or use condoms from 1 month before study start until 12 months after CAR-T cells infusion. Also, it is recommended the childbearing potential female partner uses a highly effective method of contraception for the same duration (cf. section 7.7 " Pregnancy and contraception ").
- •Patients shall be eligible to undergo CAR-T cells infusion
- •Patients consents to give blood samples.
- •Patients Patients must be located within one hour's driving distance from Gustave Roussy during the first 30 days after the injection and must be accompanied, as they should not drive during these initial 30 days
- •Specific criteria for SLE:
- •Diagnosis of SLE according to the 2019 ACR/EULAR classification criteria.
- •Patient must be positive for at least one of the following autoantibodies at screening:
- •anti-dsDNA (above the upper limit of normal, ULN) or
- •anti-Sm (above ULN) or
- •anti-nucleosome (above ULN) or
- •anti-nuclear antibodies (ANA) and a decrease of C3 or C4
- •Active severe disease with SLEDAI-2K ≥ 6
- •Inadequate response or intolerance to at least 2 immunosuppressive treatments.
- •Specific criteria for IIM:
- •Confirmed or probable diagnosis of idiopathic inflammatory myopathy (IIM) according to the 2017 EULAR/ACR classification criteria, including:
- •Dermatomyositis (DM)
- •Polymyositis (PM)
- •Immune-mediated necrotizing myopathy (IMNM)
- •Antisynthetase syndrome (ASS)
- •Patient must be positive for at least one of the autoantibodies associated with IIM or anti-nuclear antibodies at screening (See, 24.3 Appendix 3 - List of Scleroderma- and Myositis-Specific Autoantibodies )
- •Active myositis at baseline, demonstrated by at least one of the following:
- •Elevated muscle enzymes (e.g., CPK > 1.5 × upper limit of normal)
- •Manual Muscle Testing (MMT-8) score < 142/150
- •Muscle MRI or EMG showing signs of active inflammation
- •Progressive interstitial lung disease
- •Inadequate response or intolerance to at least 2 immunosuppressive treatments.
- •Specific criteria for SjD:
- •Diagnosis of SjD as per 2016 ACR-EULAR criteria
- •Documented seropositivity for SSA at screening or positive anti-nuclear antibodies associated with positive rheumatoid factor
- •Active systemic disease defined as ESSDAI >5 points
- •Refractory disease defined as inadequate response to hydroxychloroquine, glucocorticoids and oral immunosuppressive treatment, and otherwise requiring cyclophosphamide or rituximab, according to EULAR recommendations for the management of Sjogren's disease
- •History of intolerance or inadequate response to rituximab or cyclophosphamide is also permitted.
- •Specific criteria for RA
- •RA diagnosis as per ACR/EULAR 2010 classification criteria
- •Seropositivity for anti-citrullinated protein autoantibodies (ACPA) and/or rheumatoid factor (RF) at Screening
- •Treatment according to EULAR recommendation and failure of ≥2 biologic/targeted synthetic Disease Modifying Anti Rheumatic Drug (DMARDs) after failing conventional synthetic DMARD therapy (unless contraindicated)
- •Signs suggestive of active/progressive disease, defined as meeting all two below criteria at Screening:
- •At least moderate disease activity (DAS28-CRP>3.2)
- •Inflammatory activity confirmed by at least 1 swollen joints (documented by clinic or ultrasound)
- •Specific criteria for SSc:
- •Systemic sclerosis as per the 2013 ACR/EULAR Classification Criteria
- •CT scan evidence of interstitial lung disease
- 另有 3 项未显示
排除标准
- •Any significant active infection, including:
- •Active hepatitis B (defined by detectable HBV DNA) or C infection (defined by detectable HCV RNA),
- •Known HIV infection,
- •Previous treatment with any gene therapy product or CAR-T cells therapy.
- •Inadequate organ function during screening
- •Inadequate renal function is defined as eGFR ≤30mL/min/1.73m2 using the the Cockcroft-Gault Formula
- •Inadequate hepatic function is defined as any of the following:
- •defined by Child-Pugh class B or C
- •ALT and AST above 2 × ULN
- •TBL > 1.5 × ULN with the exception of participants with Gilbert's syndrome or patients with a positive Coombs test and evidence of hemolysis, who may be included if their TBL is ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN
- •International normalized ratio (INR) > 1.5
- •Inadequate cardiac function is defined as LVEF < 50% as determined by ultra-sonography performed at screening
- •Inadequate lung function requiring continuous oxygenotherapy
- •Active malignancy or history of cancer within the past 2 years (except successfully treated localized skin basal or squamous cell carcinoma, or cervical carcinoma in situ).
- •History of allogeneic hematopoietic tem cell transplantation or solid organ transplantation.
- •Pregnancy or breastfeeding.
- •Women of childbearing potential and fertile men who do not agree to use highly effective contraception or maintain sexual abstinence during the study and for 12 months after CAR-T cells infusion.
- •Any acute, severe disease flare at and during screening that needs immediate treatment other than pulse glucocorticoids and/or makes the immunosuppressive washout impossible
- •Clinically significant active, opportunistic, chronic or recurrent infection
- •Any patients requiring medications prohibited by the protocol.
研究组 & 干预措施
Treatment
Experimental
The anti-CD19 CAR-T cells will be administered as a single infusion at the dose of 1x106 cells/kg body weight
干预措施: anti-CD19 CAR-T cells (Biological)
结局指标
主要结局
Unacceptable toxicities over a period of 4 weeks after the single CAR-T cell infusion
时间窗: from CAR-T cells infusion to 30 days post-treatment
Unacceptable toxicities are defined over a period of 4 weeks after the single CAR-T cell infusion as either: * Cytokine Release Syndrome (CRS) ≥ grade 3 or, * Immune-effector Cell Associated Neurotoxicity Syndrome (ICANS) ≥ grade 3 or, * Organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) ≥ grade 3
次要结局
未报告次要终点
研究者
研究点 (1)
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