Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL

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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