The ABNL-MARRO 001 study : a phase 1-2 study of randomly allocated active myeloid target compound combinations in MDS/MPN overlap syndromes
Moyo, Tamara K. (Vanderbilt University School of Medicine)
Mendler, Jason H (University of Rochester Medical Center)
Itzykson, Raphael (Paris Diderot University)
Kishtagari, Ashwin (Vanderbilt University School of Medicine)
Solary, Eric (Institut Gustave Roussy. Université Paris-Saclay)
Seegmiller, Adam C. (Vanderbilt University School of Medicine)
Gerds, Aaron T. (Cleveland Clinic)
Ayers, Gregory D. (Vanderbilt University School of Medicine)
Dezern, Amy E. (Johns Hopkins University)
Nazha, Aziz (Cleveland Clinic)
Valent, Peter (Ludwig Boltzmann Institute for Hematology and Oncology. Medical University of Vienna)
Onida, Francesco (University of Milan)
Van Azizan de Loosdrecht, Arjan A. (Amsterdam UMC. University Medical Center)
Pleyer, Lisa (Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials)
Xicoy Cirici, Blanca (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tibes, Raoul (Mayo Clinic)
Geissler, Klaus (Sigmund Freud University)
Komrokji, Rami S. (H. Lee Moffitt Cancer Center)
Zhang, Jing (University of Wisconsin-Madison)
Germing, Ulrich (Department of Hematology. Oncology. and Clinical Immunology. University of Duesseldorf)
Steensma, David P. (Dana-Farber Cancer Institute (Boston, Estats Units d'Amèrica))
Wiseman, Daniel H. (University of Manchester)
Pfeilstöecker, Michael (Hanusch Hospital and Ludwig Boltzmann Institute for Hematology and Oncology)
Elena, Chiara (University of Pavia)
Cross, Nicholas C P (University of Southampton)
Luebbert, Michael (University of Freiburg)
Mesa, Ruben A. (Mays Cancer Center at UT Health San Antonio MD Anderson)
Montalban-Bravo, Guillermo (MD Anderson Cancer Center)
Sanz, G.F. (Hospital Universitari i Politècnic La Fe (València))
Platzbecker, Uwe (University Hospital Leipzig)
Patnaik, Mrinal M. (Mayo Clinic)
Padron, Eric (H. Lee Moffitt Cancer Center)
Santini, Valeria (University of Florence)
Fenaux, Pierre (Paris Diderot University)
Savona, Michael R. (Vanderbilt University School of Medicine)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Background: Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) comprise several rare hematologic malignancies with shared concomitant dysplastic and proliferative clinicopathologic features of bone marrow failure and propensity of acute leukemic transformation, and have significant impact on patient quality of life. The only approved disease-modifying therapies for any of the MDS/MPN are DNA methyltransferase inhibitors (DNMTi) for patients with dysplastic CMML, and still, outcomes are generally poor, making this an important area of unmet clinical need. Due to both the rarity and the heterogeneous nature of MDS/MPN, they have been challenging to study in dedicated prospective studies. Thus, refining first-line treatment strategies has been difficult, and optimal salvage treatments following DNMTi failure have also not been rigorously studied. ABNL-MARRO (A Basket study of Novel therapy for untreated MDS/MPN and Relapsed/Refractory Overlap Syndromes) is an international cooperation that leverages the expertise of the MDS/MPN International Working Group (IWG) and provides the framework for collaborative studies to advance treatment of MDS/MPN and to explore clinical and pathologic markers of disease severity, prognosis, and treatment response. Methods: ABNL MARRO 001 (AM-001) is an open label, randomly allocated phase 1/2 study that will test novel treatment combinations in MDS/MPNs, beginning with the novel targeted agent itacitinib, a selective JAK1 inhibitor, combined with ASTX727, a fixed dose oral combination of the DNMTi decitabine and the cytidine deaminase inhibitor cedazuridine to improve decitabine bioavailability. Discussion: Beyond the primary objectives of the study to evaluate the safety and efficacy of novel treatment combinations in MDS/MPN, the study will (i) Establish the ABNL MARRO infrastructure for future prospective studies, (ii) Forge innovative scientific research that will improve our understanding of pathogenetic mechanisms of disease, and (iii) Inform the clinical application of diagnostic criteria, risk stratification and prognostication tools, as well as response assessments in this heterogeneous patient population. Trial registration: This trial was registered with ClinicalTrials. gov on August 19, 2019 (Registration No. NCT04061421).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	BMC Cancer, Vol. 22 Núm. 1 (december 2022) , p. 1013, ISSN 1471-2407

DOI: 10.1186/s12885-022-10073-w
PMID: 36153475

15 p, 1.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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