Oral Arsenic Trioxide for NPM1-mutated AML

Summary

A prospective open-label phase 2 study will be designed to assess the efficacy of oral arsenic trioxide plus azacitidine in preventing relapses in patients with NPM1-mutant AML. After screening and eligibility assessment, patients will receive treatment with oral arsenic trioxide plus azacitidine for 12 months. The recruitment period will last for 24 months and it will take approximately 36 months for study completion.

Timeline

Start

2021-01-01

Primary completion

2023-12-31

Completion

2024-12-31

Publications

• Background Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G, Van Loo P, Martincorena I, Ganly P, Mudie L, McLaren S, O'Meara S, Raine K, Jones DR, Teague JW, Butler AP, Greaves MF, Ganser A, Dohner K, Schlenk RF, Dohner H, Campbell PJ. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016 Jun 9;374(23):2209-2221. doi: 10.1056/NEJMoa1516192.
• Background Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, Van Vlierberghe P, Dolgalev I, Thomas S, Aminova O, Huberman K, Cheng J, Viale A, Socci ND, Heguy A, Cherry A, Vance G, Higgins RR, Ketterling RP, Gallagher RE, Litzow M, van den Brink MR, Lazarus HM, Rowe JM, Luger S, Ferrando A, Paietta E, Tallman MS, Melnick A, Abdel-Wahab O, Levine RL. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012 Mar 22;366(12):1079-89. doi: 10.1056/NEJMoa1112304. Epub 2012 Mar 14.
• Background Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths M, Solomon E, McCaughan F, Linch DC, Gale RE, Vyas P, Freeman SD, Russell N, Burnett AK, Grimwade D; UK National Cancer Research Institute AML Working Group. Assessment of Minimal Residual Disease in Standard-Risk AML. N Engl J Med. 2016 Feb 4;374(5):422-33. doi: 10.1056/NEJMoa1507471. Epub 2016 Jan 20.
• Background Balsat M, Renneville A, Thomas X, de Botton S, Caillot D, Marceau A, Lemasle E, Marolleau JP, Nibourel O, Berthon C, Raffoux E, Pigneux A, Rodriguez C, Vey N, Cayuela JM, Hayette S, Braun T, Coude MM, Terre C, Celli-Lebras K, Dombret H, Preudhomme C, Boissel N. Postinduction Minimal Residual Disease Predicts Outcome and Benefit From Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia With NPM1 Mutation: A Study by the Acute Leukemia French Association Group. J Clin Oncol. 2017 Jan 10;35(2):185-193. doi: 10.1200/JCO.2016.67.1875. Epub 2016 Nov 14.
• Background Dillon R, Hills R, Freeman S, Potter N, Jovanovic J, Ivey A, Kanda AS, Runglall M, Foot N, Valganon M, Khwaja A, Cavenagh J, Smith M, Ommen HB, Overgaard UM, Dennis M, Knapper S, Kaur H, Taussig D, Mehta P, Raj K, Novitzky-Basso I, Nikolousis E, Danby R, Krishnamurthy P, Hill K, Finnegan D, Alimam S, Hurst E, Johnson P, Khan A, Salim R, Craddock C, Spearing R, Gilkes A, Gale R, Burnett A, Russell NH, Grimwade D. Molecular MRD status and outcome after transplantation in NPM1-mutated AML. Blood. 2020 Feb 27;135(9):680-688. doi: 10.1182/blood.2019002959.
• Background Martelli MP, Gionfriddo I, Mezzasoma F, Milano F, Pierangeli S, Mulas F, Pacini R, Tabarrini A, Pettirossi V, Rossi R, Vetro C, Brunetti L, Sportoletti P, Tiacci E, Di Raimondo F, Falini B. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells. Blood. 2015 May 28;125(22):3455-65. doi: 10.1182/blood-2014-11-611459. Epub 2015 Mar 20.
• Background El Hajj H, Dassouki Z, Berthier C, Raffoux E, Ades L, Legrand O, Hleihel R, Sahin U, Tawil N, Salameh A, Zibara K, Darwiche N, Mohty M, Dombret H, Fenaux P, de The H, Bazarbachi A. Retinoic acid and arsenic trioxide trigger degradation of mutated NPM1, resulting in apoptosis of AML cells. Blood. 2015 May 28;125(22):3447-54. doi: 10.1182/blood-2014-11-612416. Epub 2015 Mar 23.
• Background Chau D, Ng K, Chan TS, Cheng YY, Fong B, Tam S, Kwong YL, Tse E. Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9. J Hematol Oncol. 2015 May 8;8:46. doi: 10.1186/s13045-015-0143-3.

Drugs

Indications