Clinical trial NCT00259974: RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy
Official title: Double-blind Randomized Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polyneuropathy
Keywords: Anti-MAG monoclonal gammopathy
Polyneuropathy
Rituximab
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Groupe Hospitalier Pitie-Salpetriere
name: University Hospital, Bordeaux
name: University Hospital, Limoges
name: Henri Mondor University Hospital
name: University Hospital, Marseille
name: Hospices Civils de Lyon
name: University Hospital, Basel, Switzerland
First posted: 2005-12-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 82
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Polyneuropathy associated with anti-MAG monoclonal IgM gammopathy is responsive of mainly a sensory deficit in predominantly males ,aged 40-70 years. Significantly high serum anti-MAG antibodies are linked with demyelinating features of the peripheral nerves.Rituximab, an anti-CD 20 monoclonal antibody is a new drug which reduces B-lymphocytes. This study will test the safety and efficacy of rituximab in the treatment of patients with anti-MAG polyneuropathy.

Detailed description: Acting of a polyneuropathy for which there is not any treatment of reference today (see supra), a test of double-knowledge versus placebo is justified. Acting of a chronic polyneuropathy, the clinical evaluation must be led over one one year period. Acting of a sensitive polyneuropathy and the awaited benefit being the IMPROVEMENT OF the CLINICAL SIGNS, the principal criterion is a sensitive score in addition validated in chronic sensitive polyneuropathies immunodeficiency syndrome.

The patients answering the criteria of inclusion and none inclusion (see V-2) will be randomized in 2 groups: the first group will receive a perfusion IV of rituximab to the amount of 375 mg/m2 of body surface, once per week, during 4 weeks (see VII-3); the second group will receive 4 perfusions IV of placebo according to same methods'. The evaluation (see VI-1) will be carried out at the time of the randomization, then repeated in 3 months, 6 months, 9 months and 1 year.

Eligibility criteria: Inclusion Criteria:

* IgM monoclonal gammopathy
* Anti-MAG antibody titers \> 1.1000 BTU (ELISA)
* Worsening polyneuropathy with INCAT score \> 4
* Informed consent

Exclusion Criteria:

* Severe comorbidity
* Other concurrent causes of polyneuropathy
* Concurrent immunosuppressive therapies (wash-out \> 3 months)
* Previous treatment with rituximab
* Lymphoproliferative disease indicating other immunosuppressive treatment
* Unability to follow-up
* Previous documented side-effects with components involved in the tested drug
* White cell count \< 1500/mm3 or platelet count \< 75.000/mm3
* Patient under law

Primary outcomes:
measure: INCAT sensory score at 1 year
timeFrame: during de study
Secondary outcomes:
measure: Functional scales, MRC score
timeFrame: during the study
measure: Quality of life (SF 36)
timeFrame: during the study
measure: Serum lymphocytes count, IgM level, anti-MAG antibody titers
timeFrame: during the study
measure: Electrophysiological parameters
timeFrame: during the study
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpétrière, Consultation de Pathologie Neuromusculaire, Bâtiment Babinski
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Marc LEGER, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leger JM. A review of the medical management of chronic inflammatory demyelinating polyradiculoneuropathy. Expert Opin Pharmacother. 2005 Apr;6(4):569-82. doi: 10.1517/14656566.6.4.569.