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A Phase II Trial of Rituximab for Peripheral Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance (MGUS)

Phase 2
21 Years
90 Years
Not Enrolling
Precancerous Condition

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Trial Information

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
of neuropathy


Inclusion Criteria:

- Not pregnant

- Negative serum pregnancy test

- Fertile patients must use an acceptable method of birth control during treatment and
for 6 months after completion of treatment

- One of the following birth control measures must be used: birth control pills,
intrauterine device, contraceptive injections (Depo-Provera), barrier methods
such diaphragm, condom or contraceptive sponge with spermicide

- Adequate bone marrow function as indicated by sufficient precursors of all three cell
lines and cellularity of at least 20% on bone marrow biopsy within 6 months

- Platelets > 100,000/mm^3

- Absolute neutrophil count (ANC) > 1,000/mm^3

- Hemoglobin > 7 g/dL

- Serum creatinine < 3.0 mg/dL

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 times upper
limit of normal

- No history of psychiatric disorder requiring hospitalization, psychiatric
consultation, or psychotropic medications within the last year

- Patients with controlled depression are eligible, as defined by the following:

- Stable for at least 6 months

- No increase in psychotropic medications

Exclusion criteria:

- History of HIV infection or seropositivity

- History or serological profile suggesting prior hepatitis B virus (HBV) infection
(i.e., HbsAg or anti-HBs with anti-HBc)

- Prior HBV vaccination with isolated anti-HBs antibodies is not an exclusion

- HBV infection or non-vaccination-related HBV seropositivity

- Active infection

- New York Heart Association class III or IV heart disease

- History or baseline ECG tracing demonstrating severe recurrent or severe recent
(within 3 months) cardiac dysrhythmia (e.g., ventricular tachycardia, torsades de
pointes ("Twisting of the Points," a rapid polymorphic Ventricular Tachycardia), or
other serious ventricular dysrhythmias) requiring implanted defibrillator treatment

- Confirmed diagnosis of systemic lupus erythematosus (SLE)

- An isolated low titer positive antinuclear antibody test without clinical
evidence of SLE is not an exclusion criterion

- Concomitant malignancies or previous malignancies within the last five years, with
the exception of adequately treated basal cell or squamous cell carcinoma of the skin
or carcinoma in situ of the cervix

- Malignancy associated with a paraneoplastic neuropathy

- A history of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies

- A history of known severe primary or secondary immunodeficiency (e.g., common
variable immunodeficiency)

- Significant other uncontrolled medical illnesses that may interfere with drug
delivery or interpretation of results


- No live vaccine therapy within 30 days of enrollment

- No plasmapheresis within 3 months

- No high-dose intravenous immunoglobulin, chemotherapeutic agents, or high-dose
corticosteroids (> 10 mg daily or every other day) within 3 months

- No systemic corticosteroids within 3 months (unless needed for adrenal insufficiency
or at a stable dose ≤ 10 mg daily)

- No high-dose (> 250 mg/day) vitamin B6 within the past month

- No prior treatment with thalidomide or neurotoxic drugs (e.g., vinca alkaloids,
taxol, or platinum)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The proportion of patients having sustained a successful response, as measured by the neuropathy impairment score (NIS) at 6 months

Outcome Time Frame:

6 months after baseline

Safety Issue:


Principal Investigator

Benn E. Smith, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Institutional Review Board

Study ID:




Start Date:

December 2007

Completion Date:

March 2010

Related Keywords:

  • Precancerous Condition
  • monoclonal gammopathy of undetermined significance
  • Monoclonal Gammopathy of Undetermined Significance
  • Paraproteinemias
  • Peripheral Nervous System Diseases
  • Precancerous Conditions



Mayo Clinic Scottsdale Scottsdale, Arizona  85259
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905