Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders

Neuromyelitis Optica Clinical Trial

Official title:

Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02021825
• Other study ID #: MITONMO
• Status: Recruiting
• Phase: Phase 4
• First received: September 3, 2013
• Last updated: December 19, 2013
• Start date: March 2009
• Est. completion date: December 2015

Study information

• Verified date: December 2013
• Source: Xuanwu Hospital, Beijing
• Contact: Huiqing Dong, Doctor
• Phone: +86-18611786966
• Email: shshtt[@]sina.com?
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical 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 during relapses. Flow cytometric analysis, brain and spinal cord MRI was performed at baseline, 6, 12, 18, and 24 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuromyelitis Optica
• Neuromyelitis Optica Spectrum Disorders

Intervention

Drug:
• Mitoxantrone
The treatment protocol consisted of 12 mg/m2 MITO intravenous infusions every 3 months for 2 years. Dosage was adjusted according to side effects.

Locations

Country	Name	City	State
China	Department of Neurology, Xuanwu Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

References & Publications (4)

Hartung HP, Gonsette R, König 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. — View Citation

Kim 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. — View Citation

Neuhaus O, Kieseier BC, Hartung HP. Therapeutic role of mitoxantrone in multiple sclerosis. Pharmacol Ther. 2006 Jan;109(1-2):198-209. Epub 2005 Aug 10. Review. — View Citation

Weinstock-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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	one year	No
Primary	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.	six months	No
Secondary	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.	six months	Yes
Secondary	blood cell count	- Assessment of hematological system: Monitoring blood cell count regularly. Considering marrow puncture if necessary.	three months	Yes
Secondary	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.	six months	Yes