The Safety and Efficacy of YTS109 Cell for Relapsed/Refractory Autoimmune Hemolytic Anemia Patients After Receiving Three or More Lines of Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicity
研究概览
简要总结
This is a Phase I, single-arm, open-label, dose-escalation and dose-expansion study. The primary objective is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of YTS109 STAR-T cell therapy in patients with autoimmune hemolytic anemia who have failed ≥3 lines of therapy. The objective is to evaluate the safety, preliminary efficacy, pharmacokinetics/pharmacodynamics (PK/PD), and immune cell reconstitution characteristics of YTS109 cell therapy in Multi-rAIHA subjects who have failed third-line or higher-line treatments.
This study will also conduct an exploratory investigation into the impact of non-lymphodepleting conditioning prior to the infusion of STAR-T cells. For the non-lymphodepleting exploratory cell infusion, it can be administered as a single infusion or divided into 1 to 3 infusions (with the fractionated infusions to be completed within 7 days (and in any case no later than 15 days)). Dose escalation will commence at 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥12 years, regardless of gender.
- •Diagnosis of AIHA or Evans syndrome [including warm antibody, mixed AIHA and cold antibody AIHA (Cold agglutinin disease)].
- •Failure or intolerance to at least 3 lines of therapy: glucocorticoids and/or rituximab, and any one of the following treatments (splenectomy, cyclosporine, cyclophosphamide, azathioprine, mycophenolate mofetil, bendamustine, fludarabine, bortezomib, etc.Biologics, including anti-CD38 monoclonal antibody, BTK inhibitor, Syk inhibitor and complement inhibitor) (HGB < 100g/L).
- •Adequate organ function: a. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN. b. Creatinine clearance (CrCl) (Cockcroft-Gault formula) ≥60ml/min. c.Blood oxygen saturation (SpO2) ≥92%.
- •ECOG performance status≤2
- •Subjects of childbearing potential will be required to follow contraception requirements from the time of enrollment until the end of the 12-month safety follow-up period.
- •The subjects voluntarily participate in the study, sign the informed consent, demonstrate good compliance, and cooperate with follow-up.
排除标准
- •Diagnosis of lymphoproliferative tumor
- •Other hereditary or acquired hemolytic diseases (Secondary AIHA caused by drugs or infection)
- •The platelet count in peripheral blood<30×10^9/L
- •Pregnant or breast-feeding subjects
- •Receive any of the following treatments within the specified time before cell infusion: a.anti-CD20 monoclonal antibodies <12 weeks, b.sutimlimab or other marketed biologics <5 half-lives,c.plasma exchange <4 weeks, d.post-splenectomy <12 weeks, e. BTK inhibitors, anti-CD38 monoclonal antibody, Syk inhibitors, BAFF inhibitors < 5 half-lives.
- •Previously received organ or stem cell transplantation
- •History of new thrombosis or organ infarction in the past 6 months
- •Diagnosis of the active stage of the connective tissue disease.
- •Have active infections, such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection and active tuberculosis, etc.
- •Positive hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg); positive hepatitis B e antibody (HBe-Ab) or hepatitis B core antibody (HBc-Ab), and the HBV-DNA copy number is above the lower limit of the measurable capacity; positive hepatitis C (HCV) antibody; positive human immunodeficiency virus (HIV) antibody; positive syphilis test.
- •Underwent major surgery within 4 weeks before screening, as determined by the investigator to be unsuitable for enrollment.
- •Have malignant tumors within 5 years before enrollment, except tumors with negligible risk of metastasis or death and curable tumors, such as adequately treated cervical carcinoma in situ, cutaneous basal cell carcinoma, etc.
- •Have any of the following cardiovascular diseases: a.Left ventricular ejection fraction (LVEF) ≤45%, b. presence of active heart disease or congestive heart failure (New York Heart Association [NYHA] Class III or IV)), c.severe arrhythmias requiring treatment, d.have myocardial infarction, bypass surgery, or stent placement within the 6 months before the study, e.other heart diseases judged by the researcher to be unsuitable for enrollment.
- •Have a history of live attenuated vaccines within 6 weeks before enrollment.
- •Have a history of epilepsy or other active central nervous system diseases.
- •Have an allergy to the ingredients of the medicine used in this study.
- •Previously received CAR-T cell therapy.
- •Patients considered to be ineligible for the study by the investigator for reasons other than the above.
研究组 & 干预措施
YTS109 cell
Subjects will receive YTS109 cell, and dose escalation will commence at 5E6 cells/kg or the starting dose may be adjusted based on accumulated data.
干预措施: YTS109 cell (Drug)
结局指标
主要结局
Dose Limiting Toxicity
时间窗: Within 28 days after infusion
The incidence and frequency of treatment-emergent adverse events
时间窗: Within 12 months after infusion
Safety assessments are conducted using the NCI-CTCAE version 5.0 standards.
次要结局
- Best overall response rate (BOR) of each dose group(Within 12 weeks after infusion)
- Time to response (TTR)(Within 6 months after infusion)
- Area under the plasma concentration versus time curve (AUC) of YTS109(Within 12 months after infusion)
- The reconstitution of B cell in peripheral blood(Within 12 months after infusion)
- Objective response rate (ORR) of each dose group(Within 4 weeks after infusion)
- Peak Plasma Concentration (Cmax) of YTS109(Within 12 months after infusion)
- Time to Peak (Tmax) of YTS109(Within 12 months after infusion)
- Best overall response rate (BOR) of each dose group(Within 12 weeks after infusion)