Neuromyelitis OpticaPhase 4NCT02021825
Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders
A Phase 4 study testing Mitoxantrone in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders, run by Xuanwu Hospital, Beijing at 1 site in China.
Trial summary
The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects. Neurological assessment including the determination of the Expanded Disability Status Scale (EDSS) score and ophthalmologic evaluations were performed every 3 months and… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Neuromyelitis Optica, Neuromyelitis Optica Spectrum Disorders
- What is being tested?
- Mitoxantrone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- Mar 2009to Dec 2015
- Phase
- Phase 4
- 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
- Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without recurrent ON (unilateral or bilateral) but with normal brain MRI and positive serological NMO IgG antibody.
- Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without spatially limited brain lesion and positive serological NMO IgG antibody.
- NMO, fulfilled Wingerchuk 2006 Criteria for NMO.
- Patient presented at least 2 relapses during the 12 months preceding the start of mitoxantrone therapy, despite immunotherapies using corticosteroid, interferon beta, azathioprine, cyclophosphamide, Cyclosporin A, Mycophenolate Mofetil or a combination of these drugs
- Extended Disability Status Score 3-8.
- Normal range for white-blood-cell count (more than 4×109/L), neutrophil count (more than 2×109/L), and platelet count (more than 100×109/L).
Who cannot join
- Cardiac risk factors (e.g history of congestive heart failure and left ventricular ejection fraction (LVEF) < 50%
- Systemic diseases such as lupus, Sjogren's syndrome, anti-phospholipid antibody syndrome, sarcoidosis, rheumatoid arthritis, or vitamin B12 deficiency
- Previous treatment with mitoxantrone or anthracyclines
- Pregnant or planning to be pregnant
- Patients with severe liver disorders (WHO grade 4)
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Neurology, Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, 100053
Zheng Liu, Doctor, 0086-13910320552, lzwcy2003@aliyun.com
Huiqing Dong, Doctor
About this study
The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects. Neurological assessment including the determination of the Expanded Disability Status Scale (EDSS) score and ophthalmologic evaluations were performed every 3 months and during relapses. Flow cytometric analysis, brain and spinal cord MRI was performed at baseline, 6, 12, 18, and 24 months.
- Being tested
- Mitoxantrone
- Keywords
- mitoxantrone, neuromyelitis optica, relapse
- Medical subject headings
- Neuromyelitis Optica, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitoxantroneDrug
Also called Novantrone
The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects.
| Study group | Role | What they receive |
|---|---|---|
| MITO, annual relapse rate, safety | Other | For refractory NMO patients aged 18-55, the initial dose 12 mg/m2 mitoxantrone was administered over a five day course every 3 months for 2 years (a total of eight courses). The initial dose was reduced to 9 mg/m2 if the preinfusion white-blood-cell count was 3.0-3.99 ×109/L,and to 6 mg/m2 if the white-blood-cell count was 2.0-2.99 ×109/L. No infusion if the white-blood-cell count was less than 2.0×109/L. The initial dose was reduced to 10 mg/m2 for nonhaematological toxic effects of WHO grade 2-3. Subsequent dose after 3 month was reduced to 10 mg/m2 for infections that occurred within 3 weeks of a previous infusion accompanied by a white-blood-cell count below 2×109/L, or to 8 mg/m2 for infections accompanied by white-blood-cell count of less than 1×109/L. Receives: Drug: Mitoxantrone |
What is being measured
The primary outcome is the main question the study is designed to answer.
annual relapse rate (ARR)
ARR is defined as the number of confirmed relapses in a year. The number of annual relapse rate was used as parameters of effectiveness and was compared between premitoxantrone and postmitoxantrone treatment during the follow-up period.
Measured: one year
EDSS
Expanded Disability Status Scale (EDSS) scores was used as parameters of effectiveness and was compared between premitoxantrone and postmitoxantrone treatment during the follow-up period.
Measured: six months
Secondary outcomes (3)
Changes in LVEF
- Assessment of cardiac function: Changes in LVEF by transthoracic echocardiography and determination of cardiac side effects by ECG and by measurement of CK-MB, Troponin and BNP.
Measured: six months
blood cell count
- Assessment of hematological system: Monitoring blood cell count regularly. Considering marrow puncture if necessary.
Measured: three months
Flow cytometric analysis
Immunofluorescent staining of wholeblood samples were performed of blood drawing using antibodies against CD3/CD4/CD8/CD19/CD20/CD56 with isotype controls, followed by lysis of red blood cells and immediate acquisition and analysis by flow cytometry.
Measured: six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startMar 2009
- Primary completionDec 2014 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Neuromyelitis OpticaStudies of the same condition, open and under way.
- More trials run by Xuanwu Hospital, BeijingThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanwu Hospital, Beijing
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Huiqing Dong, Doctor, Principal investigator, Department of Neurology, Xuanwu Hospital, Capital Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021825
- Sponsor's protocol ID
- MITONMO
- Status last verified
- Dec 2013
- First submitted
- 3 Sep 2013
- Last updated
- 27 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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 12504397Neuhaus O, Kieseier BC, Hartung HP. Therapeutic role of mitoxantrone in multiple sclerosis. Pharmacol Ther. 2006 Jan;109(1-2):198-209. doi: 10.1016/j.pharmthera.2005.07.002. Epub 2005 Aug 10.
PubMed 16095713Kim SH, Kim W, Park MS, Sohn EH, Li XF, Kim HJ. Efficacy and safety of mitoxantrone in patients with highly relapsing neuromyelitis optica. Arch Neurol. 2011 Apr;68(4):473-9. doi: 10.1001/archneurol.2010.322. Epub 2010 Dec 13.
PubMed 21149806Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, Bakshi R. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006 Jul;63(7):957-63. doi: 10.1001/archneur.63.7.957.
PubMed 16831964
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders
- ClinicalTrials.gov ID
- NCT02021825
- Acronym / sponsor ID
- MITONMO
- Keywords
- mitoxantrone, neuromyelitis optica, relapse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Xuanwu Hospital, BeijingUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 27 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects. Neurological assessment including the determination of the Expanded Disability Status Scale (EDSS) score and ophthalmologic evaluations were performed every 3 months and during relapses. Flow cytometric analysis, brain and spinal cord MRI was performed at baseline, 6, 12, 18, and 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MITO, annual relapse rate, safety | Other | Drug: MitoxantroneFor refractory NMO patients aged 18-55, the initial dose 12 mg/m2 mitoxantrone was administered over a five day course every 3 months for 2 years (a total of eight courses). The initial dose was reduced to 9 mg/m2 if the preinfusion white-blood-cell count was 3.0-3.99 ×109/L,and to 6 mg/m2 if the white-blood-cell count was 2.0-2.99 ×109/L. No infusion if the white-blood-cell count was less than 2.0×109/L. The initial dose was reduced to 10 mg/m2 for nonhaematological toxic effects of WHO grade 2-3. Subsequent dose after 3 month was reduced to 10 mg/m2 for infections that occurred within 3 weeks of a previous infusion accompanied by a white-blood-cell count below 2×109/L, or to 8 mg/m2 for infections accompanied by white-blood-cell count of less than 1×109/L. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without recurrent ON (unilateral or bilateral) but with normal brain MRI and positive serological NMO IgG antibody.
- Recurrent longitudinal myelitis (>3 segments of spinal cord involvement by MRI) with or without spatially limited brain lesion and positive serological NMO IgG antibody.
- NMO, fulfilled Wingerchuk 2006 Criteria for NMO.
- Patient presented at least 2 relapses during the 12 months preceding the start of mitoxantrone therapy, despite immunotherapies using corticosteroid, interferon beta, azathioprine, cyclophosphamide, Cyclosporin A, Mycophenolate Mofetil or a combination of these drugs
- Extended Disability Status Score 3-8.
Key exclusion criteria (5 listed)
- Cardiac risk factors (e.g history of congestive heart failure and left ventricular ejection fraction (LVEF) < 50%
- Systemic diseases such as lupus, Sjogren's syndrome, anti-phospholipid antibody syndrome, sarcoidosis, rheumatoid arthritis, or vitamin B12 deficiency
- Previous treatment with mitoxantrone or anthracyclines
- Pregnant or planning to be pregnant
- Patients with severe liver disorders (WHO grade 4)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitoxantroneAlso: NovantroneThe treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects. | Drug | MITO, annual relapse rate, safety |
Primary outcome
annual relapse rate (ARR)
Time frame: one year
ARR is defined as the number of confirmed relapses in a year. The number of annual relapse rate was used as parameters of effectiveness and was compared between premitoxantrone and postmitoxantrone treatment during the follow-up period.
EDSS
Time frame: six months
Expanded Disability Status Scale (EDSS) scores was used as parameters of effectiveness and was compared between premitoxantrone and postmitoxantrone treatment during the follow-up period.
3 secondary outcomes
Changes in LVEF
Time frame: six months
blood cell count
Time frame: three months
Flow cytometric analysis
Time frame: six months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2013.
- Background: PubMed 12504397Hartung 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.
- Background: PubMed 16095713Neuhaus O, Kieseier BC, Hartung HP. Therapeutic role of mitoxantrone in multiple sclerosis. Pharmacol Ther. 2006 Jan;109(1-2):198-209. doi: 10.1016/j.pharmthera.2005.07.002. Epub 2005 Aug 10.
- Background: PubMed 21149806Kim SH, Kim W, Park MS, Sohn EH, Li XF, Kim HJ. Efficacy and safety of mitoxantrone in patients with highly relapsing neuromyelitis optica. Arch Neurol. 2011 Apr;68(4):473-9. doi: 10.1001/archneurol.2010.322. Epub 2010 Dec 13.
- Background: PubMed 16831964Weinstock-Guttman B, Ramanathan M, Lincoff N, Napoli SQ, Sharma J, Feichter J, Bakshi R. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol. 2006 Jul;63(7):957-63. doi: 10.1001/archneur.63.7.957.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Huiqing Dong, Doctor principal investigator
Department of Neurology, Xuanwu Hospital, Capital Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mitoxantrone in people with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders, run by Xuanwu Hospital, Beijing at 1 site in China.
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 6 inclusion and 5 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 27 Dec 2013. 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 China. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Contact Huiqing Dong, Doctor (+86-18611786966, shshtt@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
annual relapse rate (ARR) (time frame: one year). The study lists 2 primary outcomes in all. 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 NCT02021825, which also lists 4 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 27 Dec 2013.