Trial Outcomes & Findings for Rituximab in Treating Patients With Peripheral Neuropathy Caused by Monoclonal Gammopathy of Undetermined Significance (NCT NCT00588822)

Results Overview

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 neurologist measured the NIS score on both sides of the body, but recorded worst score and reported as 1 for each individual subject (i.e., each subject had only 1 reported 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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

baseline, 6 months

Results posted on

2014-05-06

Participant Flow

Subjects were enroll from January 2005 to June 2008 at the Mayo Clinic in Arizona, Florida, and Minnesota.

Participant milestones

Participant milestones
Measure	Rituximab 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Overall Study STARTED	21
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Overall Study progression of disease	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Age, Continuous	67.4 years STANDARD_DEVIATION 7.7 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants

PRIMARY outcome

Timeframe: baseline, 6 months

Population: A dichotomous measure was used so that subjects who discontinued participation prematurely could be included as non-responders.

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 neurologist measured the NIS score on both sides of the body, but recorded worst score and reported as 1 for each individual subject (i.e., each subject had only 1 reported 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.

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Subjects With at Least 10 Points Improvement in the Neuropathy Impairment Score (NIS) for Either Side of the Body at 6 Months	62 percentage of subjects Interval 38.0 to 82.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Subjects Whose Disease Has Stabilized or Responded, for Either Side of the Body, as Measured by NIS at 6 Months	86 percentage of subjects Interval 64.0 to 97.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Subjects With at Least 1 Grade Improvement in the Modified Rankin Score at 6 Months	19 percentage of subjects Interval 5.0 to 42.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Patients Having Improvement in the Hand Grip Strength Ergometry Value for Either Hand at 6 Months	52 percentage of subjects Interval 30.0 to 74.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Subjects Having One or More Stable Hand Grip Strength Ergometry Values for Either Hand at 6 Months	76 percentage of subjects Interval 53.0 to 92.0

SECONDARY outcome

Timeframe: baseline, 6 months

Monoclonal immunoglobulins measured included Immunoglobulin G (IgG), Immunoglobulin A (IgA), and Immunoglobulin M (IgM).

Outcome measures

Outcome measures
Measure	Rituximab n=21 Participants 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Percentage of Subjects With > 50% Reduction of Monoclonal Protein Titer at 6 Months IgA Responder	0 percentage of subjects Interval 0.0 to 17.0
Percentage of Subjects With > 50% Reduction of Monoclonal Protein Titer at 6 Months IgG Responder	0 percentage of subjects Interval 0.0 to 17.0
Percentage of Subjects With > 50% Reduction of Monoclonal Protein Titer at 6 Months IgM Responder	5 percentage of subjects Interval 0.0 to 25.0

Adverse Events

Rituximab

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab n=21 participants at risk 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. Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).
Cardiac disorders Myocardial infarction	4.8% 1/21 • Number of events 1 • Subjects were monitored for adverse events weekly per cycle ( Day 1, 8, 15, and 22); each subject could receive up to 2 cycles (4 infusions each.) Adverse event monitoring continued for at least 12 months following the subject's last Rituximab infusion.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Benn E. Smith

Mayo Clinic

Phone: 480-301-6711

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place