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

NCT00588822 | Terminated Phase 2 Results DMC

• 2 other identifiers: 1191-04UL1RR024150
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

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.

Conditions

Precancerous Condition

Keywords

monoclonal gammopathy of undetermined significance

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects With at Least 10 Points Improvement in the Neuropathy Impairment Score (NIS) for Either Side of the Body at 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 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.

  baseline, 6 months

Secondary Outcomes (5)

• Percentage of Subjects Whose Disease Has Stabilized or Responded, for Either Side of the Body, as Measured by NIS at 6 Months

  baseline, 6 months

• Percentage of Subjects With at Least 1 Grade Improvement in the Modified Rankin Score at 6 Months

  baseline, 6 months

• Percentage of Patients Having Improvement in the Hand Grip Strength Ergometry Value for Either Hand at 6 Months

  baseline, 6 months

• Percentage of Subjects Having One or More Stable Hand Grip Strength Ergometry Values for Either Hand at 6 Months

  baseline, 6 months

• Percentage of Subjects With > 50% Reduction of Monoclonal Protein Titer at 6 Months

  baseline, 6 months

Study Arms (1)

Rituximab

EXPERIMENTAL

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).

Biological: Rituximab

Interventions

Rituximab BIOLOGICAL

Rituximab will be given as a 375 mg/m\^2 intravenous infusion once weekly for four doses (days 1, 8, 15, and 22).

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)
• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• Genentech, Inc.: collaborator
• Biogen: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (3)

Mayo Clinic Scottsdale

Scottsdale, Arizona, 85259-5499, United States

Location

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Precancerous Conditions; Monoclonal Gammopathy of Undetermined Significance

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The study was discontinued at the first stage to the high response rate and slow accrual.

Results Point of Contact

• Title: Dr. Benn E. Smith
• Organization: Mayo Clinic

bsmith@mayo.edu

480-301-6711

Study Officials

• Benn E. Smith, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: January 9, 2008
• Study Start: January 1, 2005
• Primary Completion: January 1, 2009
• Study Completion: February 1, 2011
• Last Updated: May 6, 2014
• Results First Posted: May 6, 2014

Record last verified: 2014-04

Locations

US (3)