Efficacy and Safety of Avatrombopag in the Treatment of Thrombocytopenia After Haploidentical Hematopoietic Stem Cell Transplantation: Prospective, Multi-center, Double-blinded, Randomized Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 142
- 试验地点
- 14
- 主要终点
- the proportion of complete response(CR) on day 60 after haplo-HSCT
研究概览
简要总结
In this study, investigators aim to evaluate the efficacy of avatrombopag in thrombocytopenic patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) through a prospective, multi-center, double-blinded, randomized placebo-controlled clinical trial.
详细描述
Thrombocytopenia is a common and severe complication after haplo-HSCT, including primary isolated thrombocytopenia (PIT) and secondary failure of platelet recovery (SFPR), which may cause bleeding and infection, and thus influence the OS, DFS, and NRM of the patients. Avatrombopag has been proved effective and safe in patients with chronic liver disease(CLD) and immune thrombocytopenia (ITP) and have been approved for CLD-associated thrombocytopenia undergoing elective invasive procedure (FDA&NMPA) and ITP(FDA). Chinese consensus has recommended avatrombopag and some other thrombopoietin receptor agonists (TPO-RAs) to treat thrombocytopenia after haplo-HSCT. However, it lacks prospective studies to support that.Investigators aim to evaluate the efficacy of avatrombopag in thrombocytopenic patients after haplo-HSCT through a prospective, multi-center, double-blinded, randomized placebo-controlled clinical trial.
The patients with PLT<20×10^9/L or transfusion dependent on the 7th day (+D7) after haplo-HSCT are included and assigned in a 1:1 randomization schedule to the avatrombopag group (receiving avatrombopag, n=71）and the placebo group (receiving placebo, n=71). The primary endpoint is the proportion of participants whose PLT≥50×10^9/L on +D60 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above. Second endpoints includ the proportion of participants whose PLT≥100×10^9/L on +D60 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the proportion of participants whose PLT≥20×10^9/L and whose PLT≥50×10^9/L on +D30 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the proportion of participants whose PLT≥50×10^9/L and whose PLT≥100×10^9/L on +D90 after haplo-HSCT without the need for PLT transfusion for 7 consecutive days or above, the first day to achieve PLT≥20×10^9/L and PLT≥50×10^9/L and PLT≥100×10^9/L without the need for PLT transfusion for consecutive 7 days and above within +D60 after haplo-HSCT, the percentage of participants who need PLT transfusion and the average count of PLT from +D7 to + D60 after haplo-HSCT, the first day and the percentage of participants to achieve absolute neutrophil≥500/μL for consecutive 3 days within +D30 after haplo-HSCT, the graft-versus-host disease(GVHD), infection, the overall survival(OS),the disease free survival(DFS) and the non-relapse mortality(NRM) rates of participants within the first year after haplo-HSCT.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female, aged between 18-65 years;
- •PLT<20×10^9/L or transfusion dependent on +D7 after haplo-HSCT;
- •Agree to receive the treatment of avatrombopag after Haplo-HSCT and sign the informed consent form.
排除标准
- •With active infection;
- •ALT or AST>3ULN, or total Bil>2ULN
- •Ccr<50 mL/min;
- •With the history of arteriovenous thrombosis;
- •With history of cardiovascular disease (such as NYHA Class III/IV congestive heart failure, arrhythmia that increases the risk of thromboembolic events [such as atrial fibrillation] and angina), and subjects who have undergone coronary stent implantation, angioplasty, or coronary artery bypass grafting;
- •With treatment of drugs to promote platelet production two weekes before enrollment, including but not limited to rhTPO and TPO-RA;
- •HBsAg or anti-HCV or anti-HIV positive;
- •Known to be allergic to avatrombopag and any of its excipients;
- •With secondary or multiple HSCT;
- •Females who were pregnant or breastfeeding or who had fertile ability but refuse to take effective contraceptive measures during and one month after this trial;
- •With any other clinical trial of investigational product or device within 30 days prior to the baseline visit, except for observational study;
- •Deemed unsuitable for enrollment by the investigator for any history of or concomitant medical condition.
- •Concomitant medication:The rhIL-11, rhTPO or TPO-RA(such as eltrombopag, hetrombopag and romiplostim) and desitabine, etc. were not allowed for use during this trial.
研究组 & 干预措施
avatrombopag
Avatrombopag 20 mg/d will be taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to +D60 after haplo-HSCT. Routine treatment is allowed.
Adjustment indication:
When PLT<50×10^9/L or PLT transfusion dependent on the +D30 after haplo-HSCT, increase the dosage to 40 mg/d; When the dosage has been increased to 40 mg/d, and PLT≥80×10^9/L excluding the factor of PLT transfusion, decrease the dosage to 20 mg/d; When PLT≥80×10^9/L for 7 consecutive days excluding the factor of PLT transfusion, or PLT≥300×10^9/L excluding the factor of PLT transfusion, stop administration; When PLT<50×10^9/L or become PLT transfusion dependent after stopping administration, initiate administration again at the dosage 40 mg/d.
PLT transfusion Indication: When PLT<20×10^9/L, and/or with the symptom or risk of bleeding.
干预措施: avatrombopag (Drug)
Placebo
Placebo 20 mg/d will be taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to +D60 after haplo-HSCT. Routine treatment is allowed.
Adjustment indication:
When PLT<50×10^9/L or PLT transfusion dependent on the +D30 after haplo-HSCT, increase the dosage to 40 mg/d; When the dosage has been increased to 40 mg/d, and PLT≥80×10^9/L excluding the factor of PLT transfusion, decrease the dosage to 20 mg/d; When PLT≥80×10^9/L for 7 consecutive days excluding the factor of PLT transfusion, or PLT≥300×10^9/L excluding the factor of PLT transfusion, stop administration; When PLT<50×10^9/L or become PLT transfusion dependent after stopping administration, initiate administration again at the dosage 40 mg/d.
PLT transfusion Indication: When PLT<20×10^9/L, and/or with the symptom or risk of bleeding.
干预措施: Placebo (Drug)
结局指标
主要结局
the proportion of complete response(CR) on day 60 after haplo-HSCT
时间窗: from randomization to day 60 after haplo-HSCT
the proportion of participants whose PLT≥50×10\^9/L on day 60 after haplo-HSCT independent of PLT transfusion for 7 consecutive days or above
次要结局
- the proportion of R/CR on day 30 after haplo-HSCT(from randomization to day 30 after haplo-HSCT)
- neutrophil engraftment(from randomization to day 30 after haplo-HSCT)
- GVHD(from randomization to 1 year after haplo-HSCT)
- overall survival(OS)(from randomization to 1 year after haplo-HSCT)
- disease free survival(DFS)(from randomization to 1 year after haplo-HSCT)
- non-relapse mortality(NRM)(from randomization to 1 year after haplo-HSCT)
- the proportion of CR/remission on day 90 after haplo-HSCT(from randomization to day 90 after haplo-HSCT)
- Time to R/CR/remission(from randomization to day 60 after haplo-HSCT)
- the proportion of resonse(R)/remission on day 60 after haplo-HSCT(from randomization to day 60 after haplo-HSCT)
- PLT transfusion dependence(from randomization to day 60 after haplo-HSCT)
研究者
Xiao Hui Zhang
Vice president of Peking Univeristy Institute of Hematology
Peking University People's Hospital