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

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: Not yet recruiting
• Conditions: Acute Promyelocytic Leukaemia
• Intervention / Treatment: Drug: Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid

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: Interventional
• Enrollment (Anticipated): 109
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hao Jiang, MD; Phone Number: 13601164350; Email: 2516735116@qq.com
• Study Contact Backup: Name: Sheng ye Lu, PhD & MD; Phone Number: 15810723933; Email: lushengye01@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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.	2 year after diagnosis

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Ministry of Science and Technology of the People´s Republic of China
• Investigators: Principal Investigator: Xiao-Jun Huang, MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): August 31, 2021
• Study Completion (Anticipated): August 31, 2023

Study Registration Dates

• First Submitted: November 21, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 25, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Realgar-Indigo Naturalis Formula, Retinoic Acid
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia; Leukemia, Promyelocytic, Acute; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Arsenic Trioxide; Tretinoin
• Other Study ID 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