Rituximab in Treating Patients With Peripheral Neuropathy Caused by Monoclonal Gammopathy of Undetermined Significance
Condition: Precancerous Condition
MeSH terms: Precancerous Conditions; Peripheral Nervous System Diseases; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
Intervention: Rituximab
Intervention description: Rituximab will be given as a 375 mg/m^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 21 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: monoclonal gammopathy of undetermined significance

Summary:

      This study was done to find out if the investigational medication, rituximab, could help
      relieve the symptoms of peripheral neuropathy (such as numbness [abnormal protein in the
      blood] and weakness of the lower and upper extremities) in people who have monoclonal
      gammopathy of undetermined significance and people with a symptomatic or smoldering
      Waldestrom macroglobulinemia.

      Rituximab is an antibody which attacks a particular type of white blood cell (B Cell). By
      targeting the B-cells which make the abnormal protein which is involved in causing the nerve
      trouble, it is hoped that damage to nerve fibers will be stopped and improvement will be
      allowed to proceed.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  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

        PATIENT CHARACTERISTICS:

        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
                  criterion

          -  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

        PRIOR CONCURRENT THERAPY:

          -  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)