Efficacy and Safety of TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies Failed to First-line Treatment: a Prospective, Open-label, Nonrandomized, Multicenter Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Platelet response
研究概览
简要总结
This prospective, open-label, nonrandomized, multicenter clinical trial aims at comparing the efficacy and safety of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody vs. the best available therapy（BAT）in adult immune thrombocytopenia with autoantibodies failed (due to intolerance or resistance) to first-line treatment.
详细描述
This is a prospective, open-label, nonrandomized, multicenter clinical trial aiming at comparing the efficacy and safety of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody vs. the best available therapy（BAT）in adult immune thrombocytopenia (ITP) with autoantibodies failed (due to intolerance or resistance) to first-line treatment. The subjects include ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome.
Adult ITP patients with autoantibodies (18-65 years) will be nonrandomly divided into the following two treatment groups: 1. combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody. 2. the best available therapy（BAT）other than combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody.
The current treatment strategies and possible risks of combined use of TPO-RAs with low-dose anti-CD20 monoclonal antibody in the treatment of ITP with autoantibodies will be fully introduced to the patients by the researchers. Then the patients will be divided into one of the two groups according to the patients' will.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patients have provided written informed consent prior to enrollment.
- •18-65 years old.
- •Diagnosed as ITP secondary to connective tissue diseases (including but not limited to systemic lupus erythematosus, Sjogren's syndrome and rheumatoid arthritis), primary ITP with positive antinuclear antibody but not up to the diagnostic criteria of connective tissue diseases, primary Evans syndrome, Evans syndrome secondary to connective tissue diseases, and primary ITP with positive Coomb's test but not up to the diagnostic criteria of Evans syndrome.
- •Platelet count<30 ×10^9/L at screening.
- •Patients who have received at least one first-line treatment of ITP (glucocorticoid and / or intravenous immunoglobulin) in the past, failed (poor efficacy, or failure to maintain efficacy, or relapse), or had contraindications, intolerance, or refusal of first-line treatment.
- •Treatment for ITP (including but not limited to glucocorticoids, recombinant human thrombopoietin (rTPO)) must be completed before enrollment, or the dose must be stable or in a phase of reduction within 2 weeks before enrollment. Immunosuppressants (including but not limited to azathioprine, danazol, cyclosporine A, mycophenolate mofetil) must be finished before entering the group, or the dose must be stable or in the reduction period within 3 months before entering the group.
- •Effective contraceptive measures will be taken during the clinical trial.
排除标准
- •Thrombocytopenia secondary to thyroid disease.
- •Patients with any prior history of arterial or venous thrombosis, and with any of the following risk factors: cancer, Factor V Leiden, ATIII deficiency, and antiphospholipid syndrome.
- •Those who had received anti-CD20 monoclonal antibody within 6 months or who had previously failed to respond to low-dose anti-CD20 monoclonal antibody.
- •Patients who had failed to respond to the previous use of eltrombopag 75 mg once a day, hetrombopag 7.5mg once a day or avatrombopag 40mg once a day for more than 4 weeks.
- •Patients who have received splenectomy within one year or have splenectomy plan within one year.
- •Patients with lupus encephalopathy or lupus nephritis.
- •Patients with cataract.
- •Patients with infectious fever (including but not limited to pulmonary infection) within 1 month or with active infection during screening.
- •Existing hepatitis B virus, hepatitis C virus replication or HIV infection.
- •Patients with agranulocytosis (ANC <1× 10^9/L), or moderate and severe anemia (HGB < 90g/L). For patients with Evans syndrome, patients with HGB< 60g/L will be excluded.
- •Severe liver dysfunction (alanine aminotransferase or glutamic oxaloacetic transaminase > 3×ULN), or bilirubin level > 2×ULN except patients with Evans syndrome.
- •Patients with severe cardiac or pulmonary dysfunction.
- •Severe renal damage (creatinine clearance < 50 ml/min).
- •There were surgical planners during the study.
- •History of psychiatric disorder.
- •Pregnant or lactating women or those planning to be pregnant during the trial.
- •Patients with a history of drug/alcohol abuse (within 2 years before the study).
- •Patients that have participated in other experimental researches within one month before enrollment.
- •Any other circumstances that the investigator considers that the patient is not suitable to participate in the trial.
研究组 & 干预措施
Combined use of TPO-RAs with low-dose anti-CD20 antibody
The starting dose of eltrombopag is 50-75mg once daily. The starting dose of hetrombopag is 5.0-7.5mg once daily. The starting dose of avatrombopag is 20-40mg once daily. Prior to or within 2 weeks after initiation of TPO-RAs therapy, a single dose of Rituximab at 375mg/m2 or divided doses of Rituximab at 100mg once a week for 2-4 weeks, or a single dose of ortuzumab at 1000mg can be administered.. The dosage will be adjusted according to the results of laboratory examinations and patient tolerance.
干预措施: Combined use of TPO-RAs with low-dose anti-CD20 antibody (Drug)
The best available therapy other than combined use of TPO-RAs with low-dose anti-CD20 antibody
The best available therapy except for combined use of TPO-RAs with low-dose anti-CD20 antibody includes but not limited to glucocorticoids, intravenous immunoglobulin, recombinant human thrombopoietin, TPO receptor agonists monotherapy, rituximab monotherapy, immunosuppressants, etc., and the researchers will adjust the treatment plan at any time according to the patient's condition.
干预措施: The best available therapy (Drug)
结局指标
主要结局
Platelet response
时间窗: From the start of study treatment (Day 1) up to the end of week 24
At weeks 4-24, the proportion of subjects with platelet count (PLT) ≥30×10\^9/L and at least 2 times the baseline value in 4 out of 6 consecutive tests (at least 1 week interval between each test).
次要结局
- Platelet response(From the start of study treatment (Day 1) up to the end of week 4, 8 and 12)
- Time to platelet response(From the start of study treatment (Day 1) up to the end of week 24)
- Improvement in immune indexes(From the start of study treatment (Day 1) up to the end of week 24)
- Discontinuation rate of glucocorticoids(From the start of study treatment (Day 1) up to the end of week 24)
- Duration of platelet response(From the start of study treatment (Day 1) up to the end of week 24)
- Bleeding score(From the start of study treatment (Day 1) up to the end of week 24)
- ITP-Patient Assessment Questionnaire(From the start of study treatment (Day 1) up to the end of week 24)
- Changes of disease activity index in patients with systemic lupus erythematosus(From the start of study treatment (Day 1) up to the end of week 24)
- The improvement of symptoms(From the start of study treatment (Day 1) up to the end of week 24)
- Hemoglobin response(From the start of study treatment (Day 1) up to the end of week 24)
- functional assessment of chronic illness therapy-fatigue(From the start of study treatment (Day 1) up to the end of week 24)