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

December 20, 2007
November 5, 2012
December 2007
March 2010   (final data collection date for primary outcome measure)
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 ]
The proportion of patients having sustained a successful response, as measured by the neuropathy impairment score (NIS) at 6 months [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00588822 on ClinicalTrials.gov Archive Site
  • 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 ]
  • The proportion of patients whose disease has stabilized, as measured by NIS at 6 months [ Designated as safety issue: No ]
  • The proportion of patients with > 1 mV increase in the summated CMAP amplitude at 6 months [ Designated as safety issue: No ]
  • The proportion of patients with > 1 grade improvement in the modified Rankin Score at 6 months [ Designated as safety issue: No ]
  • The proportion of patients having improvement in the hand grip strength ergometry value for either hand at 6 months [ 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 [ Designated as safety issue: No ]
  • The proportion of patients with > 50% reduction of monoclonal protein titer at 6 months [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Rituximab in Treating Patients With Peripheral Neuropathy Caused by Monoclonal Gammopathy of Undetermined Significance
A Phase II Trial of Rituximab for Peripheral Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance (MGUS)

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Precancerous Condition
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
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.
Intervention: Biological: Rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
28
March 2010
March 2010   (final data collection date for primary outcome measure)

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)
Both
21 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00588822
1191-04
No
Alvaro Moreno Aspitia, Mayo Clinic - Jacksonville
Mayo Clinic
  • National Cancer Institute (NCI)
  • Genentech
  • Biogen Idec
Principal Investigator: Benn E. Smith, MD Mayo Clinic
Mayo Clinic
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP