Implement Randomized, Controlled, International Multi-center Clinical Trial of Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid for Non-high-risk Acute Promyelocytic Leukaemia
试验速览
- 阶段
- 3 期
- 入组人数
- 109
- 主要终点
- 2-year Event-free Survival (EFS) rate
研究概览
简要总结
Acute Promyelocytic Leukaemia (APL) has been known as a type of cancer, which is of great significance to improve its eradication rate. Recent clinical trials show that ATRA plus ATO treatment regimen can result in complete response (CR) in 90-94% of patients and 5-year disease-free survival (DFS) in more than 90% of patients. However, the ATRA plus ATO treatment regimen can achieve considerate survival rate, patients still need to receive infusion therapy in hospital. If oral arsenic can replace intravenous ATO without reduction of the efficacy, patients would not need to be administered to receive treatment, which would highly increase their quality of lives. Phase I, II Clinical trials have verified the security and efficacy of the Compound Realgar-Indigo Naturalis Formula. Compound Realgar-Indigo Naturalis Formula was approved by the China Food and Drug Administration in 2009. Investergators have done a multi-centre, randomized, controlled, non-inferiority phase 3 clinical trial in China. And the result showed that oral arsenic plus retinoic acid has an anti-leukaemic efficacy similar to the intravenous arsenic treatment. So Investigators performed an international multi-center, Randomized controlled clinical trialsto compare the efficacy of oral RIF plus ATRA with intravenous arsenic trioxide plus ATRA in patients with non-high-risk APL in different racial types.
详细描述
Acute Promyelocytic Leukaemia (APL) has been known as a type of cancer, seriously endangering human health especially for young adults. It is of great significance to improve its eradication rate. Recent clinical trials show that ATRA plus ATO treatment regimen can result in complete response (CR) in 90-94% of patients and 5-year disease-free survival (DFS) in more than 90% of patients.
However, the ATRA plus ATO treatment regimen can achieve considerate survival rate, patients still need to receive infusion therapy in hospital. If oral arsenic can replace intravenous ATO without reduction of the efficacy, patients would not need to be administered to receive treatment, which would highly increase their quality of lives. The research and development of oral arsenic has therefore become a hotpoint. Professor Huang, Shilin from he 210th Hospital of PLA, according to the Prescription Theory "Jun Chen Zuo Shi", developed and designed an oral arsenic, the Compound Realgar-Indigo Naturalis Formula. Phase I, II Clinical trials have verified the security and efficacy of the Compound Realgar-Indigo Naturalis Formula. Research Team led by Professor Huang, Saijun, Shanghai Institute of Haematology (China), studied Compound Realgar-Indigo Naturalis Formula's mechanism of action from vitro cell lines and mice.
In the following Phase II clinical trial, APL patients received Compound Realgar-Indigo Naturalis Formula solo treatment regime. It resulted in 96.7% of CR and high safety rate Compound Realgar-Indigo Naturalis Formula was approved by the China Food and Drug Administration in 2009. Investigators have done a multi-centre, randomized, controlled, non-inferiority phase 3 clinical trial in China. 242 newly diagnosed APL patients (with newly diagnosed WBC<50×10^9/L) were enrolled. And the result showed that oral arsenic plus retinoic acid has an anti-leukaemic efficacy similar to the intravenous arsenic treatment.
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
- Triple (Participant, Care Provider, Investigator)
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
- 是
入选标准
- •Newly diagnosed APL patient (with WHO performance status)
- •ALT and AST of maximum 2·5 times the ULN, and bilirubin concentration of maximum two times the ULN
- •Creatinine concentration of maximum three times the ULN
- •Performance status of 0-2 grade (ECOG)
- •WBC ≤ 10 x 109/L before the treatment
- •Informed Consent Paper signed
排除标准
- •Cerebral hemorrhage
- •Concomitant severe psychiatric condition or anything else against the fulfillment of the plan
- •Clinically significant arrhythmias or electrocardiogram abnormalities (QT>500ms)
- •Refusal to sign off the Informed Consent Paper
研究组 & 干预措施
Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
Induction: a) RIF: 60 mg/kg daily until CR, b) ATRA: 25 mg/m² daily until CR; Consolidation: a) RIF: 60 mg/kg daily, in a 4-week on 4-week off regimen for four cycles in a 4-week on 4-week off regimen for four cycles b) ATRA: 25 mg/m² daily, in a 2-week on 2-week off regimen for seven cycles
干预措施: Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid (Drug)
Arsenic trioxide Plus Retinoic Acid
Induction: a) Arsenic trioxide: 0·15 mg/kg daily until CR, b) ATRA: 25 mg/m² daily until CR Consolidation: a) Arsenic trioxide: 0.15mg/kg daily, in a 4-week on 4-week off regimen for four cycles b) ATRA: 25 mg/m² daily, in a 2-week on 2-week off regimen for seven cycles Expected Efficacy: Oral RIF plus ATRA is not inferior to intravenous arsenic trioxide plus ATRA for achieving 2-year EFS.
干预措施: Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid (Drug)
结局指标
主要结局
2-year Event-free Survival (EFS) rate
时间窗: 2 year after diagnosis
treatment failure (no CR after 45-day induction therapy, or no molecular complete remission after 3-month consolidation therapy), relapse (molecular relapse, or haematological relapse); or death from any cause.
次要结局
未报告次要终点
研究者
Xiaojun Huang,MD
Director of Hematology Department
Peking University People's Hospital