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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
PD Dr. Andrew Chan, Ruhr University of Bochum
ClinicalTrials.gov Identifier:
NCT01627938
First received: May 30, 2012
Last updated: November 4, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: Dexrazoxane (DRZ) plus Mitoxantrone (MX)
Drug: Placebo plus Mitoxantrone (MX)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Proof of Concept Study Evaluating the Reduction of Mitoxantrone-induced Cardiotoxicity and Neurological Outcome in the Combined Use of Mitoxantrone and Dexrazoxane (Cardioxane®) in Multiple Sclerosis (MSCardioPro)

Resource links provided by NLM:


Further study details as provided by Ruhr University of Bochum:

Primary Outcome Measures:
  • Changes in LVEF in the different treatment arms by cardiac MRI [ Time Frame: Baseline to month 12 ] [ Designated as safety issue: Yes ]
    Assessment of cardiac function by measurement of LVEF in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm by cardiac MRI


Secondary Outcome Measures:
  • Changes in LVEF by transthoracic echocardiography and determination of cardiac side effects by ECG and by measurement of CK-MB, Troponin and BNP in mitoxantrone plus dexrazoxane versus mitoxantrone plus placebo treatment arms [ Time Frame: Baseline and month 3,6,9,12, 24 ] [ Designated as safety issue: Yes ]
    Assessment of cardiac function by measurement of LVEF by transthoracic echocardiography, by determination of cardiac side effects by ECG and by measurement of CK-MB, Troponin and BNP in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm

  • Determination of EDSS and relapse rate in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm [ Time Frame: Baseline and month 3,6,9,12 and 24 ] [ Designated as safety issue: Yes ]
    Comparison of clinical efficacy of mitoxantrone plus dexrazoxane treatment versus mitoxantrone plus placebo treatment on neurological outcome parameters by means of EDSS and relapse rate

  • Cumulative number of active lesions by cMRI [ Time Frame: Day1 and month 12 ] [ Designated as safety issue: No ]
  • LVEF in 3D-echocardiography vs. LVEF in cardiac MRI [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
  • Clinical efficacy of DRZ+MX vs. MX monotherapy by MSFC [ Time Frame: Baseline and month 3,6,9,12 and 24 ] [ Designated as safety issue: No ]
  • Quality of Life by SF-36 questionnaire [ Time Frame: Baseline and month 3,6,9 and month 12 ] [ Designated as safety issue: No ]
  • Changes in magnetic evoked potentials: prolongation of TMCT+CMCT, potential configuration [ Time Frame: Baseline and month 3,6,9 and month 12 ] [ Designated as safety issue: No ]
  • Annual brain atrophy rates in cMRI [ Time Frame: Day 1 and month 12 ] [ Designated as safety issue: No ]
  • Changes in transcranial sonography (abnormal iron deposition AID). AID in cMRI. Comparison of both methods [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]
  • Analysis of ABD transporter gene polymorphisms as predictor of therapy response and side effect profile via TaqMan PCR [ Time Frame: Baseline and month 12 ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: April 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexrazoxane (DRZ) plus Mitoxantrone (MX)
DRZ (600 mg/m2) : MX (12 mg/m2) ratio 50:1
Drug: Dexrazoxane (DRZ) plus Mitoxantrone (MX)
Dosage: DRZ (600 mg/m2) : MX (12 mg/m2) ratio 50:1 DRZ infusion / MX infusion once every three months over a period of 12 months, i.e. 5 infusions
Other Names:
  • Cardioxane® (Dexrazoxane)
  • Ralenova® (Mitoxantrone)
Placebo Comparator: Placebo plus Mitoxantrone (MX)
Placebo + MX (12 mg/m2)
Drug: Placebo plus Mitoxantrone (MX)
MX Dosage: 12mg/m2 Placebo infusion / MX infusion once every three months over a period of 12 months, i.e. 5 infusions
Other Name: Ralenova ® (Mitoxantrone)

Detailed Description:

It is designed to provide clinical and paraclinical efficacy and safety data for dexrazoxane in Mitoxantrone treatment of Multiple Sclerosis in order to investigate the possible positive influence of dexrazoxane on cardiac function of Mitoxantrone-affected myocardial tissue and on the possible augmented clinical efficacy of Mitoxantrone in combination with dexrazoxane on neurological outcome parameters. The incidence of cardiotoxicity during combined Mitoxantrone/dexrazoxane treatment will be investigated and compared to the standard Mitoxantrone-treatment without dexrazoxane.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent to participate in the study
  • Male or female subject is 18 years of age to 55 years of age
  • Subject must have one of the below mentioned confirmed diagnoses of Multiple Sclerosis: RRMS or CPMS according to rev. McDonald Criteria (2005)
  • If female of childbearing potential: Will to practice reliable birth control measures during study treatment and for at least 6 months after completion of study medication; not lactating or pregnant; and has a documented negative pregnancy test result within 72 hours prior to study medication administration. Male study participants: Will to practice reliable birth control measures during study treatment and for at least 6 months after completion of study medication
  • Subject is willing to participate in the study, follow protocol study treatment regimen, and comply with all planned assessments
  • Mitoxantrone treatment indication is given according to current guidelines:

    • Relapsing progressive or secondary progressive MS with/without superimposed relapses
    • EDSS 3-6; EDSS deterioration ≥1 point over last 18 months or 2 relapses
    • non-response or non-tolerability of pre-treatment
  • ≥ 48 mg/m² BSA MX dose received up to baseline visit as lifetime dosage before study entry. If the patient is under regular ongoing MX treatment, the infusion interval of 3 months must be obtained (see exclusion criteria)

Exclusion Criteria:

  • Concomitant clinically suspected or confirmed neurologic disorder at study entry that may interfere with the evaluation in this protocol [i.e. EDSS, MSFC, MEP or MRI measurements]
  • Pre-Treatment with DRZ or immunosuppressive drugs of the anthracycline family with cardiotoxic potential other than MX prior to study enrollment
  • Last Treatment with MX within the past 84 days prior to study enrollment (regular 3-monthly intervals must be obtained)
  • History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive HCG laboratory test (>5 mIU/ml)
  • Unwillingness to perform adequate contraception
  • Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
  • Subjects unable or unwilling to adhere to the study-designated procedures and restrictions
  • Patients not able to perform cardiac/neurological investigations including MRI, e.g. hypersensitivity to MRI contrast agent
  • Other known contraindication for DRZ or MX according to current labelling
  • Subject has a pre-existing cardiac disease interfering with left ventricular ejection fraction, i.e. cardiac insufficience for different reasons (resulting from prior cardial conditions such as myocardial infarction, myocarditis)
  • Routine co-administration of cortisone-pulse therapy (other than for treatment of relapses), intrathecal triamcinolone-therapy or other off-label/ investigational agents (e.g. fampridine, aminopyridine)
  • History of malignancy in the past 5 years (excluding localized basal cell carcinoma of the skin)
  • Pre-Treatment with other immunosuppressive drugs (azathioprine, methotrexate, mycophenolate, cyclophosphamide) within the past 3 months
  • Pre-Treatment with monoclonal antibodies (natalizumab, rituximab) within the past 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627938

Locations
Germany
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum
Bochum, Germany, 44791
Sponsors and Collaborators
PD Dr. Andrew Chan
Investigators
Principal Investigator: Andrew Chan, PD Dr. Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum
  More Information

Publications:
Rieckmann P, Toyka KV, Bassetti C, Beer K, Beer S, Buettner U, Chofflon M, Götschi-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, Freimüller M, Kollegger H, Kristoferitsch W, Lassmann H, Markut H, Strasser-Fuchs S, Vass K, Altenkirch H, Bamborschke S, Baum K, Benecke R, Brück 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, Jügelt E, Koehler J, Kölmel W, König N, Lowitzsch K, Manegold U, Melms A, Mertin J, Oschmann P, Petereit HF, Pette M, Pöhlau 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, Wiethölter 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, Mäurer 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. Review.

Responsible Party: PD Dr. Andrew Chan, Principal Investigator, Ruhr University of Bochum
ClinicalTrials.gov Identifier: NCT01627938     History of Changes
Other Study ID Numbers: RUB001CarMS, 2010-018508-95
Study First Received: May 30, 2012
Last Updated: November 4, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Ruhr University of Bochum:
Multiple Sclerosis
MS
Mitoxantrone
Dexrazoxane
Cardioxane
cardiotoxicity
cardiac toxicity
cardiotoxic side effects
cardiac MRI
cranial MRI
LVEF
neurological outcome

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Dexrazoxane
Mitoxantrone
Razoxane
Analgesics
Antimitotic Agents
Antineoplastic Agents
Cardiotonic Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sensory System Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014