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

NCT ID: NCT04175587

Last Updated: 2019-11-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-01
• Study Completion Date: 2023-08-31

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.

Conditions

Acute Promyelocytic Leukaemia

Keywords

Realgar-Indigo Naturalis Formula, Retinoic Acid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

Group Type: EXPERIMENTAL

Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid

Intervention Type: DRUG

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.

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.

Group Type: OTHER

Compound Realgar-Indigo Naturalis Formula Plus Retinoic Acid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

intravenous arsenic trioxide plus Retinoic Acid

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ministry of Science and Technology of the People´s Republic of China

OTHER_GOV

Sponsor Role: collaborator

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Huang,MD

Director of Hematology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-Jun Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Central Contacts

Hao Jiang, MD

Role: CONTACT

Phone: 13601164350

Email: 2516735116@qq.com

Sheng ye Lu, PhD & MD

Role: CONTACT

Phone: 15810723933

Email: lushengye01@126.com

Other Identifiers

RIF & ATRA in NHR APL

Identifier Type: -

Identifier Source: org_study_id