A Phase II Trial of Rituximab for Peripheral Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance (MGUS)
- To evaluate whether rituximab therapy can produce an improvement in symptoms, signs,
and disability in patients with IgM monoclonal gammopathy of undetermined significance
(MGUS) neuropathy with or without anti-myelin-associated glycoprotein reactivity.
- To assess if patients with IgG- or IgA-associated MGUS neuropathies respond to
- To determine whether 25-foot timed walking test results correlate with neuropathy
impairment score, summated compound muscle action potential (CMAP) amplitude, or
modified Rankin scale as a measure of motor function in patients with peripheral
- To gain information regarding the toxicity of rituximab in this patient population.
OUTLINE: Patients receive rituximab IV on days 1, 8, 15, and 22. Patients with neuropathy
progression at 6 months (as indicated by an increase in the Neuropathy Impairment Score
[NIS] of ≥ 10 or a modified Rankin Score increase of > 1 grade) are taken off study.
Patients with stable or responding neuropathy (NIS of < 10 or a modified Rankin Score
increase of < 1 grade) receive a second course of rituximab. Treatment continues in the
absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed at 6 months.
- Diagnosis of monoclonal gammopathy of undetermined significance (MGUS), as evidenced
by 1 of the following criteria:
- Documented monoclonal protein in the serum (< 3 g/dL) or urine
- Monoclonal serum free light chain, with at least 50% of patients having an
immunoglobulin M (IgM) paraprotein (the balance being immunoglobulin G (IgG) or
immunoglobulin A (IgA) subtypes)
- Neuropathy Impairment Score (NIS) ≥ 25
- Stable or progressive neuropathy (i.e., not currently improving), as judged by NIS
values that have not fallen ≥ 10 (between enrollment and the last documented value),
at least 1 month but not greater than 3 months prior to enrollment
- No evidence of amyloidosis or overt lymphoma, overt myeloma, or Waldenström
macroglobulinemia with end organ damage
- No evidence of multiple myeloma, Amyloid Light-chain (AL)-amyloidosis
- No evidence of Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,
and skin changes (POEMS) syndrome, diabetes mellitus, alcohol induced neuropathy,
untreated hypothyroidism, vitamin B12 deficiency, Sjögren syndrome, and other causes
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The proportion of patients having sustained a successful response, as measured by the neuropathy impairment score (NIS) at 6 months
6 months after baseline
Benn E. Smith, MD
United States: Institutional Review Board
|Mayo Clinic Scottsdale||Scottsdale, Arizona 85259|
|Mayo Clinic - Jacksonville||Jacksonville, Florida 32224|
|Mayo Clinic Cancer Center||Rochester, Minnesota 55905|