A Prospective, One-arm and Open Clinical Study to Assess Safety and Efficacy of Anti-CD38 Antibody in the Treatment of Evans Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Safety of Anti-CD38 antibody treatment
研究概览
简要总结
A single-center, open-label, off-label use investigator-initiated clinical study with safety run-in to explore the clinical activity and safety of Anti-CD38 Antibody in adult ES patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including immunosuppressive agents, Anti-CD20 Antibody and/or TPO-RA, or those in whom no other second-line treatment options are suitable.
详细描述
Evans' syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. Due to the rarity of the disease, the treatment of ES is mostly extrapolated from what is recommended for isolated auto-immune cytopenia (AIC) and mostly relies on corticosteroids, rituximab, splenectomy, and supportive therapies.Despite continuous progress in the management of AIC and a gradual increase in ES survival, the mortality due to ES remains higher than the ones of isolated AIC, supporting the need for an improvement in ES management.
A branch of pathogenesis for ES has been revealed that plasma cells secrete pathogenic antibodies directed against platelet and red blood cell antigens. Antiplatelet specific plasma cells have been detected in the spleen of patients with rituximab refractory ITP. In those refractory cases, persistent autoreactive long-lived plasma cells in the bone marrow could explain treatment failure.
Anti-CD38 antibody, such as Daratumumab, has been developed to target tumoral plasma cells in multiple myeloma, was recently found to be effective in antibody-mediated diseases, such as autoimmune cytopenia following hematopoietic stem cell transplantation, systemic lupus and also ES.
This study will evaluate the safety and biologic activity of Anti-CD38 antibody in r/r primary ES who fail to respond to at least one previous second-line therapy or those who cannot chose suitable second-line therapy. The study will enroll approximately 10 participants. This trial will be conducted in China. All participants will be followed for at least 16 weeks after the 8 weeks of treatment.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥18 years.
- •Prior to enrollment, a clinical diagnosis of primary Evans syndrome was made.
- •Platelet count < 30×10^9/L or Hb < 100g/L or symptomatic anemia within 48 hours before the first administration of study drug;
- •Failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy or those who cannot chose other second-line therapy;
- •If receiving emergency care for ES, treatment should be stopped >2 weeks before first dose.
- •DAT positive (IgG+, with or without C3+).
- •The patient need to be in the state of active hemolysis.
- •With normal hepatic and renal functions.
- •ECOG performance status ≤
- •Cardiac function: New York Heart Association functional class ≤
- •For patients receiving maintenance treatment, corticosteroids must have a stable dose at least 2 weeks before the first administration, TPO receptor agonists and azathioprine, danazol, cyclosporin A, tacrolimus, sirolimus, etc. must be stopped at least 4 weeks before the first administration; The end of anti-CD20 antibody treatment was>6 months.The end of alkylating agent treatment was>2 months.
- •Understand the study procedures and voluntarily sign the informed consent form in person.
排除标准
- •Secondary Evans syndrome. Received any treatment of anti-CD38 antibody drug
- •Uncontrollable primary diseases of important organs, such as malignant tumors, liver failure, heart failure, renal failure and other diseases;
- •HIV positive;
- •Accompanied by uncontrollable active infection, including hepatitis B, hepatitis C, cytomegalovirus, EB virus and syphilis positive;
- •Accompanied by extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.;
- •At present, there are heart diseases, arrhythmias that need treatment or hypertension that researchers judge is poorly controlled;
- •Patients with thrombotic diseases such as pulmonary embolism, thrombosis and atherosclerosis;
- •Those who have received allogeneic stem cell transplantation or organ transplantation in the past;
- •Patients with mental disorders who cannot normally obtain informed consent and conduct trials and follow-up;
- •Patients whose toxic symptoms caused by pre-trial treatment have not disappeared;
- •Other serious diseases that may limit the subject's participation in this test (such as diabetes; Severe cardiac insufficiency; Myocardial obstruction or unstable arrhythmia or unstable angina pectoris in recent 6 months; Gastric ulcer, etc.);
- •Patients with septicemia or other irregular severe bleeding;
- •Patients taking antiplatelet drugs at the same time;
- •Pregnant women, suspected pregnancies (positive pregnancy test for human chorionic gonadotropin in urine at screening) and lactating patients.
研究组 & 干预措施
Intervention（Anti-CD38 antibody）
10 enrolled subjects : once a week x 8 doses
干预措施: Anti-CD38 antibody Injection (Drug)
结局指标
主要结局
Safety of Anti-CD38 antibody treatment
时间窗: 24 weeks
Incidence, severity, and relationship of treatment emergent adverse events after Anti-CD38 antibody treatment
Evaluation of overall efficacy response after Anti-CD38 antibody treatment within 8 weeks
时间窗: 8 weeks
Overall response rate defined as improvement in any cytopenias by at least one grade, without worsening any other cytopenias or stable disease at least once within 8 weeks after the first dose.
次要结局
- Emergency treatment(24 weeks)
- Health status survey(24 weeks)
- Measurements of Hb value at each visit time point(24 weeks)
- Measurements of hemolytic marker reticulocyte count at each visit time point(24 weeks)
- Duration of Hb response(24 weeks)
- Evaluation of stable sustained response after Anti-CD38 antibody treatment at week 8(8 weeks)
- Number of Participants With ES Response to Anti-CD38 antibody treatment(24 weeks)
- Measurements of hemolytic marker LDH at each visit time point(24 weeks)
- Measurements of hemolytic marker haptoglobin at each visit time point(24 weeks)
- Measurements of platelet count at each visit time point(24 weeks)
- Measurements of hemolytic marker total bilirubin at each visit time point(24 weeks)
- Duration of platelet response(24 weeks)
- Assessment of fatigue function in chronic disease treatment(24 weeks)
- Reduction of concomitant drug(8 weeks)
- Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale(24 weeks)