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Multiple SclerosisPhase 2MSCardioProNCT01627938

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

A Phase 2 study testing Dexrazoxane (DRZ) plus Mitoxantrone (MX) in people with Multiple Sclerosis, run by PD Dr. Andrew Chan at 1 site in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Dexrazoxane (DRZ) plus Mitoxantrone (MX)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
50 participants
Where
1 siteGermany
Study dates
Apr 2012to Apr 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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:
Show all 10Show fewer
  • 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)

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum

    Bochum, 44791

Other trials in Germany

About this study

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)

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.

Read the 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.

Being tested
Dexrazoxane (DRZ) plus Mitoxantrone (MX), Placebo plus Mitoxantrone (MX)
Keywords
Multiple Sclerosis, MS, Mitoxantrone, Dexrazoxane, Cardioxane, cardiotoxicity, cardiac toxicity, cardiotoxic side effects, cardiac MRI, cranial MRI, LVEF, neurological outcome
Medical subject headings
Multiple Sclerosis, Cardiotoxicity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dexrazoxane (DRZ) plus Mitoxantrone (MX)Drug

    Also called Cardioxane® (Dexrazoxane), Ralenova® (Mitoxantrone)

    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

  • Placebo plus Mitoxantrone (MX)Drug

    Also called Ralenova ® (Mitoxantrone)

    MX Dosage: 12mg/m2 Placebo infusion / MX infusion once every three months over a period of 12 months, i.e. 5 infusions

Study groups in NCT01627938
Study groupRoleWhat they receive
Dexrazoxane (DRZ) plus Mitoxantrone (MX)ExperimentalDRZ (600 mg/m2) : MX (12 mg/m2) ratio 50:1
Receives: Drug: Dexrazoxane (DRZ) plus Mitoxantrone (MX)
Placebo plus Mitoxantrone (MX)Placebo comparatorPlacebo + MX (12 mg/m2)
Receives: Drug: Placebo plus Mitoxantrone (MX)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in LVEF in the different treatment arms by cardiac MRI

    Assessment of cardiac function by measurement of LVEF in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm by cardiac MRI

    Measured: Baseline to month 12

Secondary outcomes (10)

  1. 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

    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

    Measured: Baseline and month 3,6,9,12, 24

  2. Determination of EDSS and relapse rate in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm

    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

    Measured: Baseline and month 3,6,9,12 and 24

  3. Cumulative number of active lesions by cMRI

    Measured: Day1 and month 12

  4. LVEF in 3D-echocardiography vs. LVEF in cardiac MRI

    Measured: Baseline and month 12

  5. Clinical efficacy of DRZ+MX vs. MX monotherapy by MSFC

    Measured: Baseline and month 3,6,9,12 and 24

  6. Quality of Life by SF-36 questionnaire

    Measured: Baseline and month 3,6,9 and month 12

  7. Changes in magnetic evoked potentials: prolongation of TMCT+CMCT, potential configuration

    Measured: Baseline and month 3,6,9 and month 12

  8. Annual brain atrophy rates in cMRI

    Measured: Day 1 and month 12

  9. Changes in transcranial sonography (abnormal iron deposition AID). AID in cMRI. Comparison of both methods

    Measured: Baseline and month 12

  10. Analysis of ABD transporter gene polymorphisms as predictor of therapy response and side effect profile via TaqMan PCR

    Measured: Baseline and month 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2012 (estimated)
  2. Study startApr 2012
  3. Primary completionApr 2015 (estimated)
  4. Study completionApr 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01627938
Sponsor's protocol ID
RUB001CarMS
Other IDs
2010-018508-95
Acronym
MSCardioPro
Status last verified
Nov 2014
First submitted
30 May 2012
Last updated
5 Nov 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 18337428

  • Morrissey SP, Le Page E, Edan G. Mitoxantrone in the treatment of multiple sclerosis. Int MS J. 2005 Nov;12(3):74-87.

    PubMed 16417821

  • 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.

    PubMed 15592728

  • 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.

    PubMed 14576518

  • 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.

    PubMed 14678264

  • 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.

    PubMed 16374818

  • 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.

    PubMed 19605531

  • 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.

    PubMed 19770476

  • 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.

    PubMed 12504397

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dexrazoxane (DRZ) plus Mitoxantrone (MX) in people with Multiple Sclerosis, run by PD Dr. Andrew Chan at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 5 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Changes in LVEF in the different treatment arms by cardiac MRI (time frame: Baseline to month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01627938, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2014; AzTrials last refreshed its copy on 30 Oct 2026.

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