Clinical trial NCT04175587: Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL
Official title: Implement Randomized, Controlled, International Multi-center Clinical Trial of Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid for Non-high-risk Acute Promyelocytic Leukaemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Promyelocytic Leukaemia
Keywords: Realgar-Indigo Naturalis Formula, Retinoic Acid
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Science and Technology of the People´s Republic of China
First posted: 2019-11-25
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a prospective, non-inferiority, randomized controlled clinical trial. The non-inferiority is concluded if the lower limit of the 95% CI for the difference in proportion of patients achieving EFS is greater than the -10% non-inferiority margin. The survival curves are estimated by using the Kaplan-Meier method and will be compared by using the log-rank test.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Newly diagnosed APL patient (with WHO performance status)
2. Age 18-70
3. ALT and AST of maximum 2·5 times the ULN, and bilirubin concentration of maximum two times the ULN
4. Creatinine concentration of maximum three times the ULN
5. Performance status of 0-2 grade (ECOG)
6. WBC ≤ 10 x 109/L before the treatment
7. Informed Consent Paper signed

Exclusion Criteria:

1. Cerebral hemorrhage
2. Pregnancy
3. Concomitant severe psychiatric condition or anything else against the fulfillment of the plan
4. Clinically significant arrhythmias or electrocardiogram abnormalities (QT\>500ms)
5. Refusal to sign off the Informed Consent Paper

Primary outcomes:
measure: 2-year Event-free Survival (EFS) rate
timeFrame: 2 year after diagnosis
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Peking University People's Hospital
name: Xiao-Jun Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: