A Randomized, Open Label, Positive Controlled, Multicenter Phase III Clinical Trial Evaluating the Efficacy and Safety of the Selected Regimen of Rovadicitinib in Moderate to Severe Chronic Graft-versus-host Disease in Third Line and Beyond
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 182
- 试验地点
- 41
- 主要终点
- Objective remission rate in the 24th week (ORR)
研究概览
简要总结
The aim of this study is to demonstrate that in subjects with moderate to severe chronic graft-versus-host disease in the third line and beyond, the use of rosuvastatin compared to the protocol chosen by the researchers can significantly improve the objective response rate of subjects at week 24.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 to 70 years old; Karnofsky (KPS) ≥ 60 points; Expected survival period exceeding 6 months;
- •Previously received allogeneic hematopoietic stem cell transplantation;
- •According to NIH standards, the clinical diagnosis is moderate to severe cGVHD；
- •Previously received systematic treatment for cGVHD with 2-5 lines;
- •Stable dosage of corticosteroids and other immunosuppressants received within 2 weeks prior to screening;
- •The main organ functions well;
- •Starting from Day 1 after enrollment in the control group of this study, participants must receive one of the drugs specified in the study protocol;
- •Female participants of childbearing age should agree to use contraceptive measures (such as intrauterine devices, birth control pills, or condoms) during the study period and for 6 months after the end of the study; Serum pregnancy test negative within 7 days prior to enrollment in the study, and must be a non lactating subject; Male participants should agree to use contraceptive measures during the study period and within 6 months after the end of the study period;
- •Subjects voluntarily joined this study, signed informed consent, and had good compliance.
排除标准
- •Has experienced or currently suffers from other malignant tumors within the past 3 years;
- •Known or suspected active aGVHD；
- •Individuals with interstitial pneumonia, non infectious pneumonia, uncontrolled active infections, or infections requiring systematic treatment within the first 7 days of randomization, except for those deemed suitable for inclusion by the researchers;
- •The occurrence and progression of other underlying diseases include post transplant lymphoid tissue proliferative diseases and recurrence of primary malignant hematological diseases;
- •Random failure of allogeneic hematopoietic stem cell transplantation within the first 6 months or having received 2 allogeneic hematopoietic stem cell transplants in the past;
- •Used JAK inhibitors, Bruton's tyrosine kinase (BTK) inhibitors, etc. within the first 2 weeks of randomization;
- •There are multiple factors that can affect oral medication, such as inability to swallow, intestinal obstruction, etc;
- •Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
- •Subjects with any severe and/or uncontrolled illnesses;
- •Individuals who are allergic to research drugs or their components;
- •Participated in other clinical trials within the first 4 weeks of randomization;
- •According to the researcher's judgment, there are accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are deemed unsuitable for inclusion due to other reasons.
研究组 & 干预措施
Rovadicitinib
Rovadicitinib: 10mg, taken orally on an empty stomach twice a day, with a minimum interval of 8 hours between each dose, and an optimal interval of 12 hours. Every 28 days is a treatment cycle.
干预措施: Rovadicitinib (Drug)
Imatinib or Methotrexate or Mycophenolate or Rituximab
Methotrexate tablets: 10mg, orally, once a week or 5mg, orally, twice a week.
Metoprolol ester: 250mg-500mg, bid, orally.
Imatinib: 100-400mg, qd, oral.
Rituximab: 375mg/m2, administered intravenously once a week for 4 consecutive weeks.
干预措施: Imatinib (Drug)
Imatinib or Methotrexate or Mycophenolate or Rituximab
Methotrexate tablets: 10mg, orally, once a week or 5mg, orally, twice a week.
Metoprolol ester: 250mg-500mg, bid, orally.
Imatinib: 100-400mg, qd, oral.
Rituximab: 375mg/m2, administered intravenously once a week for 4 consecutive weeks.
干预措施: Methotrexate (Drug)
Imatinib or Methotrexate or Mycophenolate or Rituximab
Methotrexate tablets: 10mg, orally, once a week or 5mg, orally, twice a week.
Metoprolol ester: 250mg-500mg, bid, orally.
Imatinib: 100-400mg, qd, oral.
Rituximab: 375mg/m2, administered intravenously once a week for 4 consecutive weeks.
干预措施: Mycophenolate mofetil (Drug)
Imatinib or Methotrexate or Mycophenolate or Rituximab
Methotrexate tablets: 10mg, orally, once a week or 5mg, orally, twice a week.
Metoprolol ester: 250mg-500mg, bid, orally.
Imatinib: 100-400mg, qd, oral.
Rituximab: 375mg/m2, administered intravenously once a week for 4 consecutive weeks.
干预措施: Rituximab (Drug)
结局指标
主要结局
Objective remission rate in the 24th week (ORR)
时间窗: Week 24
Researchers evaluated each organ according to the consensus criteria of the NIH 2014 conference, and at week 24, the percentage of subjects with complete response (CR) or partial response (PR) in all assessable organs was determined.
次要结局
- Best Objective Response Rate (BOR)(Week 24)
- Duration of Relief (DOR)(Through study completion, an average of 2 year)
- Improvement in Lee cGVHD symptom score of subjects in week 24(Week 24)
- Failure free survival (FFS)(Weeks 2, 4, 8, 16, 36, 48, 60, 72, 84, 96)
- Primary disease recurrence rate (MR)(Weeks 8, 16,24， 36, 48)
- Non-Relapse Mortality (NRM)(Weeks 8, 16,24， 36, 48)
- Overall survival (OS)(Through study completion, an average of 2 year)
- Percentage of subjects whose daily glucocorticoid dose decreased(Week 24)
- Changes in the Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT)(Through study completion, an average of 2 year)
- Changes in 5-level EQ-5D (EQ-5D-5L)(Through study completion, an average of 2 year)
- Adverse events (AE)(Through study completion, an average of 2 year)
- Cmax(Day 1, day 8 on cycle 1: 0.5 hour pre-dose, 0.5 hour after dose, day 1 cycle 2: 0.5 hour pre-dose, 2 hours after dose, day 1 cycle 4: 0.5 hour pre-dose, 3 hours after dose, day 1 cycle 6: 0.5 hour pre-dose, 4 hours after dose (28 days as a cycle))
- Ctrough(Day 1, day 8 on cycle 1: 0.5 hour pre-dose, 0.5 hour after dose, day 1 cycle 2: 0.5 hour pre-dose, 2 hours after dose, day 1 cycle 4: 0.5 hour pre-dose, 3 hours after dose, day 1 cycle 6: 0.5 hour pre-dose, 4 hours after dose (28 days as a cycle))