A Clinical Study Exploring the Safety, Efficacy and Cell Metabolic Dynamics of Universal CD19 / 20 Car-t Cell Injection in Moderate to Severe Refractory Systemic Lupus Erythematosus
概览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- severity of dose limiting toxicity (DLT)
概览
简要总结
This study is a single arm, open, exploratory dose escalation clinical study to evaluate the safety, efficacy, and cellular metabolic dynamics of ct1195e cells in patients with SLE.
详细描述
The study was divided into dose increasing stage and dose expanding stage.dose escalation phaseThree dose levels are tentatively determined for dose escalation: 3.0 × 108, 4.5 × 108 and 6.0 × 108 car-cd19/CD20+T cells. It is estimated that the target toxicity probability of the maximum tolerated dose is 30%, and about 12 participants are planned to be enrolled, and the number of enrolled patients in each dose group is subject to the actual situation. During the test, the researchers and partners will jointly negotiate whether to increase or decrease the dose, whether to increase to the set maximum dose group or produce the maximum available cell volume, and whether to increase the exploration of new dose level within the explored dose range (allowed to be conducted when the dose is increased or decreased) according to the participants' cell metabolism characteristics, safety, tolerance and preliminary effectiveness data, so as to determine the possible recommended therapeutic dose (RD).The DLT observation period is 28 days after the first infusion. If the treatment needs to be withdrawn before 28 days after the infusion due to disease progression or other reasons, no obvious car-t cell expansion is detected or car-t treatment is invalid, and the DLT related AE events determined by the researcher may not be related to the product, the DLT observation period can be completed before. During each dose increase, if there is a safety risk that needs to be discussed, the researchers and partners can make a dose increase/stability/decrease decision according to the safety and tolerance of participants and the metabolic kinetics of ct1192 cells. In the same dose group, the first participant had no significant safety risk 14 days after the completion of cell infusion, and subsequent participants could only carry out cell infusion.dose expansion phaseOne or more dose groups may be selected for dose expansion according to the results of the dose increasing stage to further explore the efficacy and safety in SLE patients. Each dose group and each queue plan to include up to 9 cases, and the specific number of patients in the group is subject to the actual number. DLT will not be observed in the dose expansion phase, and other research processes are the same as the dose increment phase. Researchers and collaborators will continue to monitor the safety data of the whole dose expansion phase and make decisions on admission and exit when necessary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary signing of Informed Consent Form (ICF): I fully understand and am informed of this study, and I have signed the Informed Consent Form, expressing my willingness to follow and complete all research procedures;
- •When signing the ICF, the age should be between 18 and 65 years old (inclusive), with no gender restrictions;
- •No systemic active infection (such as infectious pneumonia, tuberculosis) within 2 weeks before screening;
- •Females with fertility (defined as all females who are physiologically capable of becoming pregnant) must agree to use highly effective contraception from at least 28 days before the start of self-cleaning to 1 year after CT1195E infusion, and absolutely prohibit egg donation within 1 year after receiving study treatment during the study period. Their male partners with fertility must agree to use effective barrier contraception from the start of self-cleaning to 1 year after CT1195E infusion, and should not donate semen or sperm during the entire study period;
- •Females with fertility must have a negative serum beta-human chorionic gonadotropin (β-hCG) test result at screening and within 48 hours prior to the initiation of chemotherapy.
- •Meet the EULAR/ACR 2019 classification criteria for SLE, with a disease history of ≥6 months;
- •Prior to screening, patients must have received treatment with glucocorticoids combined with immunosuppressants (including cyclophosphamide, mycophenolate mofetil, tacrolimus, methotrexate, cyclosporine, leflunomide) and/or biologics for ≥3 months, with a stable dosage for ≥2 weeks, and the disease must still be in an active state. During screening, oral steroids must meet the following requirements:
- •If treated with hormone therapy alone, prednisone (or equivalent medication) should be ≥7.5 mg/day; When used in combination with immunosuppressants and/or biologics, there is no minimum daily dosage requirement for steroids;
- •During screening, positive for antinuclear antibody, and/or positive for anti-ds-DNA antibody, and/or positive for anti-Smith antibody;
- •During the screening period, patients with a SLEDAI-2K score of ≥7, or those with concurrent significant organ dysfunction, such as severe immune-mediated thrombocytopenia, lupus nephritis (histologically diagnosed as active nephritis type III or IV with or without type V);
排除标准
- •, blood transfusions and growth factors must not be used to meet these requirements;
- •Liver function: defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2× upper limit of normal (ULN), and total bilirubin levels ≤2× upper limit of normal (ULN)
- •Coagulation function: defined as an international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5×ULN;
- •Lung function: When exposed to indoor air, the blood oxygen saturation (SpO2) is ≥92% (measured by a pulse oximeter);
- •Cardiac function: defined as having a left ventricular ejection fraction (LVEF) of ≥50% as assessed by echocardiography (ECHO) within the 8 weeks prior to screening.
- •Exclusion Criteria:
- •Those who have suffered from severe lupus nephritis within the previous 2 months and require hemodialysis, or have received prednisone ≥100 mg/d or equivalent hormone treatment for ≥14 days;
- •Those who have undergone plasma exchange, plasma separation, hemodialysis within the previous 30 days, or those who have suffered from lupus crisis within the previous 30 days;
- •Screen for individuals with a history of ≥ Grade 2 bleeding within the previous 30 days or those requiring long-term anticoagulant therapy;
- •History of any of the following cardiovascular diseases within 30 days prior to screening: heart failure of NYHA class III or IV, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant heart diseases;
研究组 & 干预措施
CT1195E CAR-T cells Injection
CT1195E cells infusion
干预措施: CAR-T Therapy (Other)
结局指标
主要结局
severity of dose limiting toxicity (DLT)
时间窗: Within 28 days after infusion
Incidence of dose limiting toxicity (DLT)
时间窗: Within 28 days after infusion
Evaluate the maximum tolerable dose (MTD) and/or dose range of ct1195E
时间窗: After medication to day 28
Ct1195E MTD and/or dose range
severity of adverse events (AES)
时间窗: Within 180 days after infusion
Incidence of adverse events (AES)
时间窗: Within 180 days after infusion
次要结局
- Proportion of participants with SLE responder index (sri-4)(1, 2,3, 6, 9 and 12 months after drug use)
- Proportion of participants with low lupus disease activity status (lldas)(1, 2,3, 6, 9 and 12 months after drug use)
- Proportion of participants achieving disease remission (doris)(1, 2, 3, 6, 9 and 12 months after drug use)
- Changes of SLE disease activity index (sledai-2k) score from baseline after medication(1,2,3,6,9 and 12 months after drug use)
- After treatment, the SLE disease activity index (Selena - SLEDAI) score changed from baseline(1, 2, 3, 6, 9 and 12 months after drug use)
- After treatment, the index of lupus erythematosus assessment group (bilag-2004) changed from baseline(1, 2, 3, 9 and 12 months after drug use)
- The SLE activity score (sle-das) changed from baseline after treatment(1, 2, 3, 9 and 12 months after drug use)
- Changes in clinicians' overall judgment (PGA) score from baseline after medication(1, 2, 3, 9 and 12 months after drug use)
- Proportion of patients without other SLE therapy after medication(1, 2, 3, 9 and 12 months after drug use)
- Changes in immunoglobulin (IgG, IgM, IgA) levels during medication(1, 2, 3, 9 and 12 months after drug use)
- The change value of post medication Health Assessment Questionnaire Disability Index (HAQ-DI) from baseline(1, 2, 3, 9 and 12 months after drug use)
- duration of ct1195E gene in blood(Within 1 year after CAR-T cell infusion)
- Copy numbe of ct1195E gene in blood(Within 1 year after CAR-T cell infusion)
- Changes of B cell functional subsets (initial B cells, memory B cells, plasma cells) after ct1195E infusion(Within 1 year after CAR-T cell infusion)
研究者
Qiubai Li
Director, Head of Department of Rheumatology and Immunology, Principal Investigator, Professor, Wuhan Union Hospital
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology