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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

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

Brief 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.

Detailed Summary:

This was a Phase II single arm trial evaluating the use of Rituximab administered at standard dose and schedule as an initial cycle of therapy, followed by a re-evaluation at 6 months.

If progression in neuropathy (as indicated by an increase in the Neuropathy Impairment Score (NIS) of greater than or equal to 10 or a modified Rankin Score increase of > 1 grade) the patient was off study. In addition, if the subject elected to pursue other active treatment including but not limited to plasmapheresis, high-dose intravenous immuneglobulin (IVIG), chemotherapeutic agents, or high dose corticosteroids, or if conditions in the exclusion criteria develop subsequent to enrollment, the subject was off study.

If the neuropathy is stable or responding (NIS of < 10 or a modified Rankin Score increase of < 1 grade) the patient would have received Cycle 2 of rituximab followed by a reevaluation at 12 months.

The study had a Simon Optimal two-stage Phase II design (α 5%, β 10%, π0 5%, π1 20%). The minimum clinically important response rate was 20%. The first stage was to include 21 patients and the second stage a total of 41 patients. The treatment would be rejected if there were fewer than 2 responders at the first stage or fewer than 5 responders at the second stage. The treatment would be accepted for further study if there were at least 5 responders out of 41 patients.

Current Primary Outcome: Percentage of Subjects With at Least 10 Points Improvement in the Neuropathy Impairment Score (NIS) for Either Side of the Body at 6 Months [ Time Frame: baseline, 6 months ]

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

Current Secondary Outcome:

• Percentage of Subjects Whose Disease Has Stabilized or Responded, for Either Side of the Body, as Measured by NIS at 6 Months [ Time Frame: baseline, 6 months ]

  The Neuropathy Impairment Score (previously called the Neurologic Disability Score [NDS]) is derived from a neurologic examination obtained in a standard way by a specially trained neurologist. Decisions are based on the neurologist's judgment of what is normal considering site, age, sex, weight, height, and physical fitness. The instrument has 35 items, each ranked for left and right sides of the body; weakness is scored 0=normal, 1=25% disability, 2=50% disability, 3=75% disability and 4=100% disability. NIS total score was calculated as the sum of the 35 items, ranging from 0 to 140, with higher score indicating greater disability or impairment.

  The NIS score was measured on both sides of the body, the worst score recorded reported as 1 for each individual subject. Stability was defined as change of less than 10 points in the NIS total score. Improvement was defined as at least 10 points improvement in NIS total score, that is, reduction in the number of points on the scale.

• Percentage of Subjects With at Least 1 Grade Improvement in the Modified Rankin Score at 6 Months [ Time Frame: baseline, 6 months ]
  The Modified Rankin Scale was used to determine functional disability as follows: 0 = asymptomatic; 1 = symptoms not interfering with manual activities/walking normally; 2 = minor difficulties in manual activities/walking independently without support; 3 = unable to perform some manual activities/walking independently with support; 4 = unable to eat, dress or wash independently/needing assistance to walk; 5 = no useful tasks performed with upper limbs/confined to wheelchair. Therefore, scores could range from 0 to 5, with higher values indicating greater disability.
• Percentage of Patients Having Improvement in the Hand Grip Strength Ergometry Value for Either Hand at 6 Months [ Time Frame: baseline, 6 months ]
  Grip strength was measured by a dynamometer in both hands at baseline and every three months until the final study visit. Response criteria was defined as achieving improvement in hand grip strength dynamometry values (>10% better relative to baseline at the 6 month visit on either side).
• Percentage of Subjects Having One or More Stable Hand Grip Strength Ergometry Values for Either Hand at 6 Months [ Time Frame: baseline, 6 months ]
  Grip strength was measured by a dynamometer in both hands at baseline and every three months until the final study visit. Response criteria was defined as achieving stable hand grip strength dynamometry values (no more than 10% better or worse relative to baseline at the 6 month visit on either side).
• Percentage of Subjects With > 50% Reduction of Monoclonal Protein Titer at 6 Months [ Time Frame: baseline, 6 months ]
  Monoclonal immunoglobulins measured included Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM).

Original Secondary Outcome:

• The proportion of patients whose disease has stabilized, as measured by NIS at 6 months
• The proportion of patients with > 1 mV increase in the summated CMAP amplitude at 6 months
• The proportion of patients with > 1 grade improvement in the modified Rankin Score at 6 months
• The proportion of patients having improvement in the hand grip strength ergometry value for either hand at 6 months
• The proportion of patients having one or more stable hand grip strength ergometry values for either hand at 6 months
• The proportion of patients with > 50% reduction of monoclonal protein titer at 6 months

Dates:
Date Received: December 20, 2007
Date Started: January 2005
Date Completion:
Last Updated: April 3, 2014
Last Verified: April 2014