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

November 26, 2019 updated by: Xiaojun Huang,MD, Peking University People's Hospital

Implement Randomized, Controlled, International Multi-center Clinical Trial of Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid for Non-high-risk Acute Promyelocytic Leukaemia

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
109

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 66 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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
Drug: Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
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.
Other Names:
  • intravenous arsenic trioxide plus Retinoic Acid
Other: 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.
Drug: Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid
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.
Other Names:
  • intravenous arsenic trioxide plus Retinoic Acid

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
2-year Event-free Survival (EFS) rate
Time Frame: 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.
2 year after diagnosis

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University People's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ministry of Science and Technology of the People´s Republic of China

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Xiao-jun Huang, MD, Peking University People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2021

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 21, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 25, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 29, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 26, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RIF & ATRA in NHR APL

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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