A Investigator-initiated Clinical Trial to Assess Safety and Efficacy of Daratumumab in the Treatment of Relapsed/Refractory Primary Immune Thrombocytopenia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Evaluate of response after daratumumab treatment
研究概览
简要总结
A single-center, open-label, off-label use investigator-initiated clinical study to explore the clinical activity and safety of daratumumab in adult ITP patients who have not responded adequately or relapsed after first-line treatment and at least one second-line therapy including rituximab and/or TPO-RA.
详细描述
Primary immune thrombocytopenia is an autoimmune disease associated with a reduced peripheral blood platelet count. The first-line treatment is corticosteroids. Splenectomy, rituximab, and thrombopoietin receptor agonists (TPO RAs, such as Etrapopar and Romistine) are commonly used as second-line therapy. However, many of the treatments used achieve few lasting remissions. About 20% - 30% of patients have inadequate or no response to first-line and second-line treatment, and would develop into recurrent/refractory (r/r) ITP.
A branch of pathogenesis for ITP 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.
Daratumumab, an anti-CD38 monoclonal antibody 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 ITP.
This study will evaluate the safety and biologic activity of Daratumumab in r/r primary ITP who fail to respond to at least one previous second-line therapy. The study will enroll approximately 20 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.
- •Diagnosed with ITP that has persisted for ≥3 months and with a platelet count of <30 X 109/L measured within 2 days prior to inclusion.
- •Failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab and/or TPO-RA.
- •If receiving emergency care for ITP, treatment should be stopped >2 weeks before first dose.
- •A positive result to the ELISA test to detect antibody against GPIIb/IIIa or GPIIb/IIIa and GPIb/IX within 1 week prior to inclusion.
- •With normal hepatic and renal functions.
- •ECOG Performance Status ≤
- •February 16, 2023 After approval by the Ethics Committee on , subjects no longer require platelet glycoprotein autoantibodies positivity upon enrollment.
排除标准
- •Received any treatment of anti-CD38 antibody drug.
- •Has been diagnosed with malignancy and/or liver failure, heart failure and renal failure.
- •Known previous infection or seropositivity for HIV, Hepatitis B, Hepatitis C, Cytomegalovirus, EB virus, Syphilis.
- •Any clinically overt hemorrhage.
- •Has been diagnosed with cardiac disease, arrhythmia and/or severe or uncontrollable hypertension
- •Known pulmonary embolism, thrombosis and/or atherosclerosis.
- •Has been received allogeneic stem cell transplantation or organ transplantation.
- •Patients with history of current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
- •Pregnancy or lactation.
研究组 & 干预措施
Intervention
Daratumumab once a week x 8 doses
干预措施: Daratumumab Injection (Drug)
结局指标
主要结局
Evaluate of response after daratumumab treatment
时间窗: 8 weeks
The proportion of patients with 2 consecutive platelet counts of ≥ 50×109/L within 8 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of daratumumab
时间窗: 24 weeks
Incidence, severity, and relationship of treatment emergent adverse events after daratumumab treatment
次要结局
- Time to first platelet count of ≥50 × 109/L without salvage therapy.(24 weeks)
- The proportion of subjects receiving rescue medications(24 weeks)
- Changes in immunoglobulin levels(24 weeks)
- The proportion of patients with ≥2 consecutive platelet counts (separated by ≥7 days) of ≥30 × 109/L and a ≥2-fold increase from the baseline count within 8 weeks(8 weeks)
- Overall response rate at week 8 and week 24(24 weeks)
- Complete response rate at week 8 and week 24(24 weeks)
- Cumulative response duration of platelet count of ≥30 × 109/L and a platelet count doubling from the baseline within 24 weeks(24 weeks)
- Durable sustained platelet count response rate(24 weeks)
- WHO bleeding score at baseline and at week 8 and 24 after treatment(24 weeks)
- The proportion of subjects with concomitant medication reduction or discontinuation(24 weeks)