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

November 4, 2014 updated by: PD Dr. Andrew Chan

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bochum, Germany, 44791
        • Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Ralenova ® (Mitoxantrone)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in LVEF in the different treatment arms by cardiac MRI
Time Frame: Baseline to month 12
Assessment of cardiac function by measurement of LVEF in mitoxantrone plus dexrazoxane treatment arm versus mitoxantrone plus placebo treatment arm by cardiac MRI
Baseline to month 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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
Baseline and month 3,6,9,12, 24
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
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
Baseline and month 3,6,9,12 and 24
Cumulative number of active lesions by cMRI
Time Frame: Day1 and month 12
Day1 and month 12
LVEF in 3D-echocardiography vs. LVEF in cardiac MRI
Time Frame: Baseline and month 12
Baseline and month 12
Clinical efficacy of DRZ+MX vs. MX monotherapy by MSFC
Time Frame: Baseline and month 3,6,9,12 and 24
Baseline and month 3,6,9,12 and 24
Quality of Life by SF-36 questionnaire
Time Frame: Baseline and month 3,6,9 and month 12
Baseline and month 3,6,9 and month 12
Changes in magnetic evoked potentials: prolongation of TMCT+CMCT, potential configuration
Time Frame: Baseline and month 3,6,9 and month 12
Baseline and month 3,6,9 and month 12
Annual brain atrophy rates in cMRI
Time Frame: Day 1 and month 12
Day 1 and month 12
Changes in transcranial sonography (abnormal iron deposition AID). AID in cMRI. Comparison of both methods
Time Frame: Baseline and month 12
Baseline and month 12
Analysis of ABD transporter gene polymorphisms as predictor of therapy response and side effect profile via TaqMan PCR
Time Frame: Baseline and month 12
Baseline and month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PD Dr. Andrew Chan

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrew Chan, PD Dr., Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2012

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2015

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 30, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RUB001CarMS
  • 2010-018508-95 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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