A Multicenter, Randomized, Open-label Study To Compare The Efficacy And Safety Of Eltrombopag Combining Rituximab With Eltrombopag In Adult ITP Patients
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 224
- 试验地点
- 1
- 主要终点
- Treatment response
研究概览
简要总结
This multicenter randomized, open-label study aimed to compare the efficacy and safety of eltrombopag combining rituximab with eltrombopag in China adult ITP patients .This study was be conducted in adult ITP patients who had not responded to or had relapsed after previous treatment of ITP, including first line therapy and /or splenectomy.
详细描述
The primary objective of this study was to evaluate the efficacy and safety of eltrombopag combining rituximab treating previously treated ITP patients compared to eltrombopag. The secondary objective was to evaluate the efficacy of eltrombopag combining rituximab in ITP patients with positive autoantibody compared to eltrombopag .In addition, health-related quality of life (HRQoL) measure was assessed in all participants.
224 eligible subjects were randomized to either eltrombopag combining rituximab or eltrombopag treatment in 1:1 ratio. 112 enrolled patients are randomly picked up to take eltrombopag combining with rituximab at the indicated dose. 112 enrolled patients are randomly picked up to take eltrombopag at the indicated dose.
The initial dose of eltrombopag administration was an oral 75 mg once daily in all participants .The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24.
Subjects in eltrombopag combining rituximab treatment group received single dose infusion of rituximab 375 mg/m(2) within 14 days after enrollment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •Age from 18 to 60 years old
- •Diagnosed with ITP and have a platelet count of <30 ×10^9/L on Day 1 (or within 48 hours prior to dosing on Day 1).
- •Patients who have no response or relapsed after splenectomy(at least more than 6 months). Or patients who have not been splenectomised and have either not responded to one or more prior therapies, or who have relapsed prior therapy.
- •Subjects treated with previous therapy(including but not limited to corticosteroid, azathioprine, danazol, cyclosporin A, mycophenolate mofetil) must have been completed prior to randomization, or must not be increasing a dose after enrollment.
- •No pre-existing cardiac disease within the last 3 months. No arrhythmia known to increase the risk of thrombolic events (e.g. atrial fibrillation), or patients with a Corrected QT interval (QTc) >450msec or QTc >480 for patients with a Bundle Branch Block.
- •No pre-existing infection within the last 1 months(including but not limited to pulmonary infection)
- •Laboratory tests for coagulation function showed that prothrombin time (PT/INR) and activated partial thromboplastin time (APTT) no exceed normal by more than 20%. No history of clotting disorder, other than ITP.
- •White blood cell count, neutrophil absolute value, hemoglobin, within the reference range, with the following exceptions:
- •Hemoglobin: females and males 10.0 g/dl are eligible for inclusion,
- •Absolute neutrophil count (ANC) ≥1500/µL (1.5×109/L) is required for inclusion
- •The following blood chemistry test result no exceed normal by more than 20%:alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine,serum albumin must not be below the lower limit of normal (LLN) by more than 10%.
- •Subject is non-childbearing potential of childbearing potential and use acceptable methods of contraception throughout the study.
- •Subjects fully understand and are able to comply with the requirements of the research protocol and are willing to complete the study as planned.
排除标准
- •Patients with any prior history of arterial or venous thrombosis, and with following risk factors: cancer, Factor V Leiden, ATIII deficiency, antiphospholipid syndrome.
- •Pregnant or lactating women;
- •Subjects is currently receiving treatment with another study medication.
- •Any laboratory or clinical evidence for HIV infection.
- •Any clinical history for hepatitis C infection; chronic hepatitis B infection; or any evidence for active hepatitis at the time of subject screening. Laboratory test shows positive serology for Hepatitis C or Hepatitis B (HB). In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
- •History of platelet aggregation that prevents reliable measurement of platelet counts.
- •Any clinically relevant abnormality, other than ITP,which in the opinion of the investigator makes the subject unsuitable for participation in the study.
研究组 & 干预措施
efficacy of eltrombopag combining rituximab
After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.
All subjects receive single dose infusion of rituximab 375 mg/m(2) within 14 days after enrollment.
Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.
干预措施: eltrombopag combining rituximab (Drug)
efficacy of eltrombopag
After enrollment,all subjects receive eltrombopag treatment,the initial dose of eltrombopag administration was an oral 75 mg once daily.Complete blood count including platelet count was done once a week.The dose of eltrombopag was adjusted according to the subject platelet count during the period from week 1 to week 24. If the platelet count >250×10^9/L, the eltrombopag will stop until the platelet count <30×10^9/L.
Efficacy and safety will be evaluated at Week 4, Week 8, and Week 12.
干预措施: eltrombopag (Drug)
结局指标
主要结局
Treatment response
时间窗: From the start of study treatment (Day 1) up to the end of week 12.
Number of participants achieving a platelet count \>=30×10\^9/L and at least doubling of the baseline count at Week 4, Week 8, and Week 12 .
次要结局
- Drug efficacy(From the start of study treatment (Day 1) up to the end of week 4, week 8 and week 12.)
- Long-term treatment response(From the start of study treatment (Day 1) up to the end of week 16, week 20 and week 24)
- Time to Response(From the start of study treatment (Day 1) up to the end of week 24)
- Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale.(From the start of study treatment (Day 1) up to the end of week 24.)
- Evaluation of effectiveness(From the start of study treatment (Day 1) up to the end of week 24.)
- Duration of response(From the start of study treatment (Day 1) up to the end of week 24.)
- Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)(From the start of study treatment (Day 1) up to the end of week 24.)
- Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)(From the start of study treatment (Day 1) up to the end of week 24.)
- Number of Participants with side effects of the drugs(From the start of study treatment (Day 1) up to the end of week 24.)
研究者
Zhang Lei
Professor/Vice director of Thrombosis &Hemostasis Center
Institute of Hematology & Blood Diseases Hospital, China