Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma

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Publishe Ahea of Print on February 20, 2015, as oi:10.3324/haematol.2014.119735. Copyright 2015 Ferrata Storti Founation. Phase I/II Stuy of the Combination of Panobinostat an Carfilzomib in Patients with Relapse/Refractory Multiple Myeloma by Jesus G. Bereja, Lowell L. Hart, Joseph R. Mace, Ewar R. Arrowsmith, James H. Essell, Rami S. Owera, John D. Hainsworth, an Ian W. Flinn Haematologica 2015 [Epub ahea of print] Citation: Bereja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, an Flinn IW. Phase I/II Stuy of the Combination of Panobinostat an Carfilzomib in Patients with Relapse/Refractory Multiple Myeloma. Haematologica. 2015; 100:xxx oi:10.3324/haematol.2014.119735 Publisher's Disclaimer. E-publishing ahea of print is increasingly important for the rapi issemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have complete a regular peer review an have been accepte for publication. E-publishing of this PDF file has been approve by the authors. After having E-publishe Ahea of Print, manuscripts will then unergo technical an English eiting, typesetting, proof correction an be presente for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal isclaimers that apply to the journal also pertain to this prouction process.

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Supplemental Text Methos Supplement Cariac Exclusion Criteria Patients with impaire cariac function, incluing a history or presence of sustaine ventricular tachyarrhythmia, any history of ventricular fibrillation or Torsae e pointes, braycaria efine as HR <50 bpm, screening ECG with a QTc >450 msec, right bunle branch block + left anterior hemiblock (bifascicular block, myocarial infarction or unstable angina within 6 months of treatment, an other clinically significant heart isease (e.g. CHF NY Heart Association class III or IV, uncontrolle hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) were exclue from this stuy. No formal cariac testing other than EKG was require for stuy participation. Dose-limiting toxicities Definitions Dose limiting toxicities for the Phase I portion of the stuy were efine as Grae 4 neutropenia for >7 ays or febrile neutropenia, Grae 4 thrombocytopenia or Grae 3 thrombocytopenia with Grae 2 bleeing, Grae 3 or 4 non-hematologic toxicity (excluing alopecia) espite optimal supportive care lasting > 72 hours or requiring a ose reuction in the first cycle, an any toxicity that prevente a patient from receiving at least 75% of the require oses of both carfilzomib an panobinostat.