Brief Title
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
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
2-year Event-free Survival (EFS) rate
Condition
Acute Promyelocytic Leukaemia
Intervention
Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
Study Arms / Comparison Groups
Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
109
Start Date
December 1, 2019
Completion Date
August 31, 2023
Primary Completion Date
August 31, 2021
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
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Xiao-Jun Huang, MD, 13601164350, [email protected]
Administrative Informations
NCT ID
NCT04175587
Organization ID
RIF & ATRA in NHR APL
Responsible Party
Principal Investigator
Study Sponsor
Peking University People's Hospital
Collaborators
Ministry of Science and Technology of the People´s Republic of China
Study Sponsor
Xiao-Jun Huang, MD, Principal Investigator, Peking University People's Hospital
Verification Date
November 2019