The ABNL-MARRO 001 study: a phase 1–2 study of randomly allocated active myeloid target compound combinations in MDS/MPN overlap syndromes
Year: 2022
Type: article
Study design: Study Protocol
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).
Source: BMC Cancer
Authors: Tamara K. Moyo, Jason H. Mendler, Raphael Itzykson, Ashwin Kishtagari, Eric Solary, Adam C. Seegmiller, Aaron T. Gerds, Gregory D. Ayers, Amy E. Dezern, Aziz Nazha, Peter Valent, Arjan A. van de Loosdrecht, Francesco Onida, Lisa Pleyer, Blanca Xicoy Cirici, Raoul Tibes, Klaus Geissler, Rami S. Komrokji, Jing Zhang, Ulrich Germing, David P. Steensma, Daniel H. Wiseman, Michael Pfeilstöecker, Chiara Elena, Nicholas C. P. Cross, Jean-Jacques Kiladjian, Michael Luebbert, Ruben A. Mesa, Guillermo Montalban-Bravo, Guillermo F. Sanz, Uwe Platzbecker, Mrinal M. Patnaik, Eric Padron, Valeria Santini, Pierre Fenaux, Michael R. Savona, On Behalf of the MDS/MPN International Working Group
Institutions: Vanderbilt University, Levine Cancer Institute, Vanderbilt-Ingram Cancer Center, University of Rochester Medicine, Université Paris Diderot, Université Paris-Saclay, Institut Gustave Roussy, Cleveland Clinic, Johns Hopkins University, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Amsterdam UMC Location Vrije Universiteit Amsterdam, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Paracelsus Medical University, Universitat Autònoma de Barcelona, Josep Carreras Leukaemia Research Institute, Institut Català d'Oncologia, Mayo Clinic in Arizona, Sigmund Freud Privatuniversität Wien, Moffitt Cancer Center, University of Wisconsin–Madison, Heinrich Heine University Düsseldorf, Dana-Farber Cancer Institute, University of Manchester, Hanusch Hospital, University of Pavia, University of Southampton, Inserm, Université Paris Cité, Hôpital Saint-Louis, Centre d'Investigation Clinique Saint-Louis, University of Freiburg, Mays Cancer Center at UT Health San Antonio, The University of Texas MD Anderson Cancer Center, Hospital Universitari i Politècnic La Fe, University Hospital Leipzig, Mayo Clinic, University of Florence
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,790
OpenAlex ID: W4296970967