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Precancerous ConditionPhase 2NCT00588822

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

A Phase 2 study testing Rituximab in people with Precancerous Condition, run by Mayo Clinic at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 21 to 90 years
Conditions the study is for
Precancerous Condition
What is being tested?
Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
3 sitesUnited States
Study dates
Jan 2005to Feb 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic - Jacksonville

    Jacksonville, Florida, 32224

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona, 85259-5499

Other trials in United States

About this study

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

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.

Read the detailed description

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.

Being tested
Rituximab
Keywords
monoclonal gammopathy of undetermined significance
Medical subject headings
Precancerous Conditions, Monoclonal Gammopathy of Undetermined Significance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabBiological

    Also called Rituxan

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

Study groups in NCT00588822
Study groupRoleWhat they receive
RituximabExperimentalSubjects 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).
Receives: Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: baseline, 6 months

Secondary outcomes (5)

  1. Percentage of Subjects Whose Disease Has Stabilized or Responded, for Either Side of the Body, as Measured by NIS 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 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.

    Measured: baseline, 6 months

  2. Percentage of Subjects With at Least 1 Grade Improvement in the Modified Rankin Score at 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.

    Measured: baseline, 6 months

  3. Percentage of Patients Having Improvement in the Hand Grip Strength Ergometry Value for Either Hand at 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).

    Measured: baseline, 6 months

  4. Percentage of Subjects Having One or More Stable Hand Grip Strength Ergometry Values for Either Hand at 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).

    Measured: baseline, 6 months

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

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

    Measured: baseline, 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2008 (estimated)
  2. Study startJan 2005
  3. Primary completionJan 2009
  4. Study completionFeb 2011

Why it stopped: Discontinuation due to the high response rate at the 1st stage and slow accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00588822
Sponsor's protocol ID
1191-04
Other IDs
UL1RR024150
Status last verified
Apr 2014
First submitted
20 Dec 2007
Last updated
6 May 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab in people with Precancerous Condition, run by Mayo Clinic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 6 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00588822.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2014.

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