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

Phase 4

• Conditions: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorders
• Interventions: Drug: Mitoxantrone

• Registration Number: NCT02021825
• Lead Sponsor: Xuanwu Hospital, Beijing

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2013-09-03
• Status Verified: 2013-12
• Study First Submitted QC: 2013-12-19
• Last Update Submitted: 2013-12-19
• Study First Posted: 2013-12-27
• Last Update Posted: 2013-12-27
• Primary Completion: 2014-12
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MITO, annual relapse rate, safety	Mitoxantrone	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.

Primary Outcome Measures

Name	Time	Method
EDSS	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.
annual relapse rate (ARR)	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.

Secondary Outcome Measures

Name	Time	Method
Changes in LVEF	six months	- 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.
blood cell count	three months	- Assessment of hematological system: Monitoring blood cell count regularly. Considering marrow puncture if necessary.
Flow cytometric analysis	six months	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.

Trial Locations

Locations (1)

Department of Neurology, Xuanwu Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China