Rituximab in Treating Patients With Peripheral Neuropathy Caused by Monoclonal Gammopathy of Undetermined Significance

This study has been completed.
Sponsor:
Collaborators:
Genentech
Biogen Idec
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00588822
First received: December 20, 2007
Last updated: November 5, 2012
Last verified: November 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block abnormal cell growth in different ways. Some block the ability of abnormal cells to grow and spread. Others find abnormal cells and help kill them or carry cell-killing substances to them.

PURPOSE: This phase II trial is studying how well rituximab works in treating patients with peripheral neuropathy caused by monoclonal gammopathy of undetermined significance.


Condition Intervention Phase
Precancerous Condition
Biological: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Rituximab for Peripheral Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance (MGUS)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • The proportion of patients having sustained a successful response, as measured by the neuropathy impairment score (NIS) at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The proportion of patients whose disease has stabilized, as measured by NIS at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]
  • The proportion of patients with > 1 millivolt (mV) increase in the summated CMAP amplitude at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]
  • The proportion of patients with > 1 grade improvement in the modified Rankin Score at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]
  • The proportion of patients having improvement in the hand grip strength ergometry value for either hand at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]
  • The proportion of patients having one or more stable hand grip strength ergometry values for either hand at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]
  • The proportion of patients with > 50% reduction of monoclonal protein titer at 6 months [ Time Frame: 6 months after baseline ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: December 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MGUS subjects
Subjects diagnosed with Monoclonal Gammopathy of Undetermined Significance (MGUS). Subjects will receive rituximab administered at the standard dose and schedule as an initial cycle of therapy, followed by a re-evaluation at 6 months. If the neuropathy is stable or responding at 6 months, the subject will receive Cycle 2 of rituximab, followed by a re-evaluation at 12 months.
Biological: Rituximab
Rituximab will be given as a 375 mg/m^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Other Name: Rituxan

Detailed Description:

OBJECTIVES:

  • 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 rituximab.
  • 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 neuropathy.
  • 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.

  Eligibility

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00588822

Locations
United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Genentech
Biogen Idec
Investigators
Principal Investigator: Benn E. Smith, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Alvaro Moreno Aspitia, Mayo Clinic - Jacksonville
ClinicalTrials.gov Identifier: NCT00588822     History of Changes
Other Study ID Numbers: 1191-04
Study First Received: December 20, 2007
Last Updated: November 5, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
monoclonal gammopathy of undetermined significance

Additional relevant MeSH terms:
Monoclonal Gammopathy of Undetermined Significance
Paraproteinemias
Peripheral Nervous System Diseases
Precancerous Conditions
Hypergammaglobulinemia
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuromuscular Diseases
Nervous System Diseases
Neoplasms
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014