A Clinical Trial to Assess the Efficacy and Safety of the Combination of a Drug Call Quizartinib With Chemotherapy (FLAG-IDA) in Patients With Acute Myeloid Leukemia That Has Not Responded to the First Treatment or That Has Returned After the First Treatment

Summary

This is a multicenter, prospective, non-randomized, Phase I-II trial to assess the efficacy and safety of the combination of oral quizartinib and FLAG-IDA chemotherapy schedule (FLAG-QUIDA regimen) in first relapsed/refractory AML (acute myeloid leukemia) patients.

Timeline

Start

2019-12-26

Primary completion

2023-12

Completion

2023-12

Publications

• Background Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Lowenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
• Background Forman SJ, Rowe JM. The myth of the second remission of acute leukemia in the adult. Blood. 2013 Feb 14;121(7):1077-82. doi: 10.1182/blood-2012-08-234492. Epub 2012 Dec 14.
• Background Estey EH. Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia. 2000 Mar;14(3):476-9. doi: 10.1038/sj.leu.2401568.
• Background Yavuz S, Paydas S, Disel U, Sahin B. IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. Am J Ther. 2006 Sep-Oct;13(5):389-93. doi: 10.1097/01.mjt.0000181690.21601.09.
• Background Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V. FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol. 2003 Apr;82(4):231-5. doi: 10.1007/s00277-003-0624-2. Epub 2003 Mar 15.
• Background de la Rubia J, Regadera A, Martin G, Cervera J, Sanz G, Martinez J, Jarque I, Garcia I, Andreu R, Moscardo F, Jimenez C, Molla S, Benlloch L, Sanz M. FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res. 2002 Aug;26(8):725-30. doi: 10.1016/s0145-2126(02)00003-6.
• Background Kim H, Park JH, Lee JH, Lee JH, Joo YD, Lee WS, Bae SH, Mo Ryoo H, Lee KH; Cooperative Study Group A for Hematology. Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: a prospective, multicenter phase II study. Am J Hematol. 2009 Mar;84(3):161-6. doi: 10.1002/ajh.21351.
• Background Bergua JM, Montesinos P, Martinez-Cuadron D, Fernandez-Abellan P, Serrano J, Sayas MJ, Prieto-Fernandez J, Garcia R, Garcia-Huerta AJ, Barrios M, Benavente C, Perez-Encinas M, Simiele A, Rodriguez-Macias G, Herrera-Puente P, Rodriguez-Veiga R, Martinez-Sanchez MP, Amador-Barciela ML, Riaza-Grau R, Sanz MA; PETHEMA group. A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol. 2016 Sep;174(5):700-10. doi: 10.1111/bjh.14107. Epub 2016 Apr 26.
• Background Cortes J, Perl AE, Dohner H, Kantarjian H, Martinelli G, Kovacsovics T, Rousselot P, Steffen B, Dombret H, Estey E, Strickland S, Altman JK, Baldus CD, Burnett A, Kramer A, Russell N, Shah NP, Smith CC, Wang ES, Ifrah N, Gammon G, Trone D, Lazzaretto D, Levis M. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):889-903. doi: 10.1016/S1470-2045(18)30240-7. Epub 2018 May 31.
• Background Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3.
• Background Cortes JE, Tallman MS, Schiller GJ, Trone D, Gammon G, Goldberg SL, Perl AE, Marie JP, Martinelli G, Kantarjian HM, Levis MJ. Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD-mutated, relapsed or refractory AML. Blood. 2018 Aug 9;132(6):598-607. doi: 10.1182/blood-2018-01-821629. Epub 2018 Jun 6.
• Background Chen Y, Pan Y, Guo Y, Zhao W, Ho WT, Wang J, Xu M, Yang FC, Zhao ZJ. Tyrosine kinase inhibitors targeting FLT3 in the treatment of acute myeloid leukemia. Stem Cell Investig. 2017 Jun 2;4:48. doi: 10.21037/sci.2017.05.04. eCollection 2017.
• Background Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.
• Background Creutzig U, Kaspers GJ. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2004 Aug 15;22(16):3432-3. doi: 10.1200/JCO.2004.99.116. No abstract available.
• Background Montesinos P, Lorenzo I, Martin G, Sanz J, Perez-Sirvent ML, Martinez D, Orti G, Algarra L, Martinez J, Moscardo F, de la Rubia J, Jarque I, Sanz G, Sanz MA. Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model. Haematologica. 2008 Jan;93(1):67-74. doi: 10.3324/haematol.11575.
• Bernal T, Zambrano Marquez J, Rodriguez-Veiga R, Rodriguez-Arboli E, Bergua-Burgues JM, Vives S, Arnan M, Martinez Sanchez P, Herrera-Puente P, Serrano-Lopez J, Rubio V, Marchante-Cepillo I, Cervera-Calvo M, Novo Garcia A, Fernandez Martin R, Gil Cortes C, Rodriguez-Medina C, Noriega-Concepcion V, Alfonso-Pierola A, Loredo C, Antuna-Casal M, Boluda B, Cano-Ferri I, Acuna-Cruz E, Torres-Minana L, Sanchez-Garcia J, Bilbao C, Gomez-Casares MT, Martinez Cuadron D, Montesinos P. Quizartinib in Combination With FLAG-IDA for Relapsed or Refractory Acute Myeloid Leukemia (FLAG-QUIDA): A PETHEMA Phase I-II Trial. Am J Hematol. 2026 Jun 29. doi: 10.1002/ajh.70424. Online ahead of print.

Drugs

Indications