Clinical trial NCT02021825: Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders
Official title: Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Neuromyelitis Optica
Neuromyelitis Optica Spectrum Disorders
Keywords: mitoxantrone
neuromyelitis optica
relapse
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2013-12-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: annual relapse rate (ARR)
timeFrame: one year
measure: EDSS
timeFrame: six months
Secondary outcomes:
measure: Changes in LVEF
timeFrame: six months
measure: blood cell count
timeFrame: three months
measure: Flow cytometric analysis
timeFrame: six months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Neurology, Xuanwu Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University
name: Huiqing Dong, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Neuhaus 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.
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.
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. doi: 10.1001/archneur.63.7.957.