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

Primary Purpose

Acute Promyelocytic Leukaemia

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
Sponsored by
Peking University People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Promyelocytic Leukaemia focused on measuring Realgar-Indigo Naturalis Formula, Retinoic Acid

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Other

    Arm Label

    Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid

    Arsenic trioxide Plus Retinoic Acid

    Arm 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

    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.

    Outcomes

    Primary Outcome Measures

    2-year Event-free Survival (EFS) rate
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    November 21, 2019
    Last Updated
    November 26, 2019
    Sponsor
    Peking University People's Hospital
    Collaborators
    Ministry of Science and Technology of the People´s Republic of China
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04175587
    Brief Title
    Randomized,International Multi-center Clinical Trial of RIF Plus RA for Non-high-risk APL
    Acronym
    RIF
    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

    2. Study Status

    Record Verification Date
    November 2019
    Overall Recruitment Status
    Unknown status
    Study Start Date
    December 1, 2019 (Anticipated)
    Primary Completion Date
    August 31, 2021 (Anticipated)
    Study Completion Date
    August 31, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Peking University People's Hospital
    Collaborators
    Ministry of Science and Technology of the People´s Republic of China

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Promyelocytic Leukaemia
    Keywords
    Realgar-Indigo Naturalis Formula, Retinoic Acid

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    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.
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    109 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
    Arm Type
    Experimental
    Arm 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
    Arm Title
    Arsenic trioxide Plus Retinoic Acid
    Arm Type
    Other
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
    Other Intervention Name(s)
    intravenous arsenic trioxide plus Retinoic Acid
    Intervention Description
    Randomization is done centrally according to trial centers Eligible patients are randomly assigned (2:1) to the Treatment Group or the Control Group, with a 24-month follow-up.
    Primary Outcome Measure Information:
    Title
    2-year Event-free Survival (EFS) rate
    Description
    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.
    Time Frame
    2 year after diagnosis

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Newly diagnosed APL patient (with WHO performance status) Age 18-70 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 Exclusion Criteria: Cerebral hemorrhage Pregnancy 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Hao Jiang, MD
    Phone
    13601164350
    Email
    2516735116@qq.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sheng ye Lu, PhD & MD
    Phone
    15810723933
    Email
    lushengye01@126.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Xiao-Jun Huang, MD
    Organizational Affiliation
    Peking University People's Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

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

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