Study to Evaluate the Reduction of Cardiac Problems in Multiple Sclerosis Patients With Mitoxantrone and Dexrazoxane in Combination

Summary

This study will primarily address the question whether the combination of Mitoxantrone therapy with dexrazoxane can reduce cardiotoxic side effects in the treatment of Multiple Sclerosis patients in comparison to Mitoxantrone monotherapy.

Timeline

Start

2012-04

Primary completion

2015-04

Completion

2016-04

Publications

• Background Flachenecker P, Meissner H. Fatigue in multiple sclerosis presenting as acute relapse: subjective and objective assessment. Mult Scler. 2008 Mar;14(2):274-7. doi: 10.1177/1352458507082480.
• Background Morrissey SP, Le Page E, Edan G. Mitoxantrone in the treatment of multiple sclerosis. Int MS J. 2005 Nov;12(3):74-87.
• Background Rieckmann P, Toyka KV, Bassetti C, Beer K, Beer S, Buettner U, Chofflon M, Gotschi-Fuchs M, Hess K, Kappos L, Kesselring J, Goebels N, Ludin HP, Mattle H, Schluep M, Vaney C, Baumhackl U, Berger T, Deisenhammer F, Fazekas F, Freimuller M, Kollegger H, Kristoferitsch W, Lassmann H, Markut H, Strasser-Fuchs S, Vass K, Altenkirch H, Bamborschke S, Baum K, Benecke R, Bruck W, Dommasch D, Elias WG, Gass A, Gehlen W, Haas J, Haferkamp G, Hanefeld F, Hartung HP, Heesen C, Heidenreich F, Heitmann R, Hemmer B, Hense T, Hohlfeld R, Janzen RW, Japp G, Jung S, Jugelt E, Koehler J, Kolmel W, Konig N, Lowitzsch K, Manegold U, Melms A, Mertin J, Oschmann P, Petereit HF, Pette M, Pohlau D, Pohl D, Poser S, Sailer M, Schmidt S, Schock G, Schulz M, Schwarz S, Seidel D, Sommer N, Stangel M, Stark E, Steinbrecher A, Tumani H, Voltz R, Weber F, Weinrich W, Weissert R, Wiendl H, Wietholter H, Wildemann U, Zettl UK, Zipp F, Zschenderlein R, Izquierdo G, Kirjazovas A, Packauskas L, Miller D, Koncan Vracko B, Millers A, Orologas A, Panellus M, Sindic CJ, Bratic M, Svraka A, Vella NR, Stelmasiak Z, Selmaj K, Bartosik-Psujik H, Mitosek-Szewczyk K, Belniak E, Mochecka A, Bayas A, Chan A, Flachenecker P, Gold R, Kallmann B, Leussink V, Maurer M, Ruprecht K, Stoll G, Weilbach FX; Multiple Sclerosis Therapy Consensus Group. Escalating immunotherapy of multiple sclerosis--new aspects and practical application. J Neurol. 2004 Nov;251(11):1329-39. doi: 10.1007/s00415-004-0537-6.
• Background Spindler M, Weilbach F, Beer M, Sandstede J, Kostler H, Strotmann J, Voelker W, Hahn D, Ertl G, Gold R. Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity in patients with multiple sclerosis. J Cardiovasc Pharmacol. 2003 Nov;42(5):680-7. doi: 10.1097/00005344-200311000-00015.
• Background Weilbach FX, Chan A, Toyka KV, Gold R. The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2004 Jan;135(1):49-55. doi: 10.1111/j.1365-2249.2004.02344.x.
• Background Bernitsas E, Wei W, Mikol DD. Suppression of mitoxantrone cardiotoxicity in multiple sclerosis patients by dexrazoxane. Ann Neurol. 2006 Jan;59(1):206-9. doi: 10.1002/ana.20747.
• Background Cotte S, von Ahsen N, Kruse N, Huber B, Winkelmann A, Zettl UK, Starck M, Konig N, Tellez N, Dorr J, Paul F, Zipp F, Luhder F, Koepsell H, Pannek H, Montalban X, Gold R, Chan A. ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis. Brain. 2009 Sep;132(Pt 9):2517-30. doi: 10.1093/brain/awp164. Epub 2009 Jul 15.
• Background Dorr J, Bitsch A, Schmailzl KJ, Chan A, von Ahsen N, Hummel M, Varon R, Lill CM, Vogel HP, Zipp F, Paul F. Severe cardiac failure in a patient with multiple sclerosis following low-dose mitoxantrone treatment. Neurology. 2009 Sep 22;73(12):991-3. doi: 10.1212/WNL.0b013e3181b878f6. No abstract available.
• Background Hartung HP, Gonsette R, Konig N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T; Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002 Dec 21-28;360(9350):2018-25. doi: 10.1016/S0140-6736(02)12023-X.

Drugs

Indications