Treatment of Non-high-risk Acute Promyelocytic Leukemia (APL) With Realgar-Indigo Naturalis Formula (RIF)

NCT ID: NCT02899169

Last Updated: 2021-09-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-01
• Study Completion Date: 2022-11-01

Brief Summary

The investigators design a multicenter randomized controlled trial to prove that RIF plus ATRA is possibly superior to ATO plus ATRA as consolidation and maintenance treatment for the patients with non-high-risk APL.

Detailed Description

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) which accounts for 10-15% of acute myeloid leukemia. It is characterized by the PML-RARA fusion gene generated by the t(15;17)(q22;q21) chromosomal translocation. The application of ATRA and ATO, make APL from highly fatal to highly curable. APL0406 study proves that ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with non-high-risk APL. Now, the arsenic trioxide has already became the based regimen as targeted first-line treatment without chemotherapy. A study shows that oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as maintenance treatment of APL. The investigators design a multicenter randomized controlled trial to prove that RIF plus ATRA is possibly superior to ATO plus ATRA as consolidation and maintenance treatment for the patients with non-high-risk APL. Application of oral RIF decrease the total hospitalization days.

Conditions

Acute Promyelocytic Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral Realgar-Indigo naturalis formula(RIF) Group

Induction therapy: ATO and ATRA, which will maintain until complete hematologic remission. Hydroxyurea should be administrated until WBC count decrease \<10x109/L. Consolidation therapy: RIF（60mg/kg/d) and ATRA 4 weeks on and 2 weeks off, until the fusion gene expression is negative. Maintenance therapy: RIF and ATRA 2 weeks on and 2 weeks off for a total of 6 courses.

Group Type: EXPERIMENTAL

Realgar-Indigo naturalis formula

Intervention Type: DRUG

all-trans retinoic acid

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

Intravenous Arsenic Trioxide(ATO) Group

Induction therapy: ATO and ATRA, which will maintain until complete hematologic remission. Hydroxyurea should be administrated until WBC count decrease \<10x109/L. Consolidation therapy: ATO and ATRA 4 weeks on and 2 weeks off, until the fusion gene expression is negative. Maintenance therapy: ATO and ATRA 2 weeks on and 2 weeks off for a total of 6 courses.

Group Type: ACTIVE_COMPARATOR

all-trans retinoic acid

Intervention Type: DRUG

Arsenic trioxide

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

Interventions

Realgar-Indigo naturalis formula

Intervention Type: DRUG

all-trans retinoic acid

Intervention Type: DRUG

Arsenic trioxide

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

Other Intervention Names

RIF; ATRA; Tretinoin; ATO; Trisenox (R); As2O3

Eligibility Criteria

Inclusion Criteria

• age 14 to 70 years
• Newly diagnosed APL with t(15;17)(q22;q12)
• Before treatment the Peripheral blood white blood cell count≤10×109/L
• Patients who can complete the entire treatment process
• Patients or their families signed written informed consent

Exclusion Criteria

• Be allergic to the drug ingredient, the supplementary material or the allergic constitution person
• Cardiac insufficiency, renal insufficiency, significant arrhythmias, EKG abnormalities or other important organ dysfunction
• Combined with other malignant tumors
• Pregnant and lactating women
• Participants in other drug trials in the last 3 months
• Suffering from mental illness or other circumstances which unable to carry out the plan
• Other patients who were not suitable for the study

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tang-Du Hospital

OTHER

Sponsor Role: collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Huaiyu Wang, Dr.

Role: STUDY_CHAIR

First Affiliated Hospital Xi'an Jiaotong University

Locations

First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Huaiyu Wang, Dr.

Role: CONTACT

whymed@126.com

15809207527

Facility Contacts

Huaiyu Wang, Dr.

Role: primary

whymed@126.com

15809207527

References

Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, Ferrara F, Fazi P, Cicconi L, Di Bona E, Specchia G, Sica S, Divona M, Levis A, Fiedler W, Cerqui E, Breccia M, Fioritoni G, Salih HR, Cazzola M, Melillo L, Carella AM, Brandts CH, Morra E, von Lilienfeld-Toal M, Hertenstein B, Wattad M, Lubbert M, Hanel M, Schmitz N, Link H, Kropp MG, Rambaldi A, La Nasa G, Luppi M, Ciceri F, Finizio O, Venditti A, Fabbiano F, Dohner K, Sauer M, Ganser A, Amadori S, Mandelli F, Dohner H, Ehninger G, Schlenk RF, Platzbecker U; Gruppo Italiano Malattie Ematologiche dell'Adulto; German-Austrian Acute Myeloid Leukemia Study Group; Study Alliance Leukemia. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874.

Reference Type: RESULT

PMID: 23841729 (View on PubMed)

Zhu HH, Wu DP, Jin J, Li JY, Ma J, Wang JX, Jiang H, Chen SJ, Huang XJ. Oral tetra-arsenic tetra-sulfide formula versus intravenous arsenic trioxide as first-line treatment of acute promyelocytic leukemia: a multicenter randomized controlled trial. J Clin Oncol. 2013 Nov 20;31(33):4215-21. doi: 10.1200/JCO.2013.48.8312. Epub 2013 Oct 14.

Reference Type: RESULT

PMID: 24127444 (View on PubMed)

Zhu HH, Huang XJ. Oral arsenic and retinoic acid for non-high-risk acute promyelocytic leukemia. N Engl J Med. 2014 Dec 4;371(23):2239-41. doi: 10.1056/NEJMc1412035. No abstract available.

Reference Type: RESULT

PMID: 25470713 (View on PubMed)

Platzbecker U, Avvisati G, Cicconi L, Thiede C, Paoloni F, Vignetti M, Ferrara F, Divona M, Albano F, Efficace F, Fazi P, Sborgia M, Di Bona E, Breccia M, Borlenghi E, Cairoli R, Rambaldi A, Melillo L, La Nasa G, Fiedler W, Brossart P, Hertenstein B, Salih HR, Wattad M, Lubbert M, Brandts CH, Hanel M, Rollig C, Schmitz N, Link H, Frairia C, Pogliani EM, Fozza C, D'Arco AM, Di Renzo N, Cortelezzi A, Fabbiano F, Dohner K, Ganser A, Dohner H, Amadori S, Mandelli F, Ehninger G, Schlenk RF, Lo-Coco F. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial. J Clin Oncol. 2017 Feb 20;35(6):605-612. doi: 10.1200/JCO.2016.67.1982. Epub 2016 Oct 31.

Reference Type: RESULT

PMID: 27400939 (View on PubMed)

Chen S, Qin W, Lu X, Liu L, Zheng Y, Lu X, Wang X, Zhang X, Gong S, Wei S, Zhang H, Ding H, Seifollah R, Li J, Zhang H, Wu D, Abiona O, He P, Zhang R, Wald D, Wang H. Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial. Haematologica. 2025 Mar 1;110(3):621-628. doi: 10.3324/haematol.2024.285905.

Reference Type: DERIVED

PMID: 39506905 (View on PubMed)

Zhang X, Liu L, Yao Y, Gong S, Wang M, Xi J, Chen L, Wei S, Zhang H, Zhao C, Wang H. Treatment of non-high-risk acute promyelocytic leukemia with realgar-indigo naturalis formula (RIF) and all-trans retinoid acid (ATRA): study protocol for a randomized controlled trial. Trials. 2020 Jan 2;21(1):7. doi: 10.1186/s13063-019-3983-2.

Reference Type: DERIVED

PMID: 31898521 (View on PubMed)

Other Identifiers

XJTU1AF2016LSL-017

Identifier Type: -

Identifier Source: org_study_id