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

Capital Medical University

Status and phase: Unknown; Phase 4

Conditions: Neuromyelitis Optica; Neuromyelitis Optica Spectrum Disorders

Treatments: Drug: Mitoxantrone

Study type: Interventional

Funder types: Other

Identifiers

NCT02021825

MITONMO

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

MITO, annual relapse rate, safety

Other group

Description:

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.

Treatment:

Drug: Mitoxantrone