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

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.

Timeline

Start

2016-09-01

Primary completion

2022-09-01

Completion

2022-11-01

Outcome

Met primary endpoint

paper the ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, [P<0.01] PMID 39506905 ↗

Publications

• Results 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.
• Results 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.
• Results 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.
• Results 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.
• 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.
• 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.

Drugs

Indications