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Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03701711
Recruitment Status : Recruiting
First Posted : October 10, 2018
Last Update Posted : October 19, 2020
Celgene Corporation
University of Michigan
Information provided by (Responsible Party):
Bakri Elsheikh, Ohio State University

Brief Summary:
Anti-myelin-associated glycoprotein (MAG) is a rare autoimmune disorder of the peripheral nerves that presents with weakness, gait imbalance, and loss of sensation. It almost always occurs in the setting of excess protein buildup in the body in the form of immunoglobulin monoclonal (IgM) gammopathy. Anti-MAG neuropathy currently has no established therapies. It is diagnosed through blood tests (anti-MAG and IgM), nerve conduction studies (which showed marked velocity slowing), and clinical exam findings.The efficacy of lenalidomide has been demonstrated in anti-MAG peripheral neuropathy with two separate dosing regimens: 25mg on days 1-21 of each 28 day cycle in conjunction with oral dexamethasone 20mg/day on days 1-4 of each cycle as well as at 5mg on days 1-21 of each cycle without oral dexamethasone. This phase 1 study aims to determine the maximum tolerated dose (MTD) of Lenalidomide in patients with anti-MAG neuropathy. We will explore preliminary efficacy and postulate that this drug is effective in this subset of patients, using preselected, specifically tailored outcome measures that encompass quality of life, neurologic function, serum protein levels, and focused measures of proprioception.

Condition or disease Intervention/treatment Phase
Demyelinating Sensorimotor Neuropathy Drug: Lenalidomide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm dose escalation study
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase I Study of Lenalidomide in Combination With Dexamethasone in Anti-MAG Demyelinating Sensorimotor Neuropathy
Actual Study Start Date : September 10, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Lenalidomide escalation and expansion
Among the participants who will be receiving lenalidomide, the first 12 participants will be in the dose escalation phase; with the subsequent 8 participants anticipated to receive dose expansion.
Drug: Lenalidomide

Dose Escalation

Patients in the dose escalation phase will receive oral treatment with:

Lenalidomide: 10, 15, or 25 mg on Days 1-21 of every 28-day cycle Dexamethasone: 20mg on Days 1,8,15 and 22

Starting doses of Lenalidomide will be assigned at the time of registration.

Dose Expansion

Once the MTD has been established or determined, 8 additional patients will be treated at the MTD of lenalidomide at the same schedule as above. Dexamethasone will be given at the same dose as in the dose escalation portion of the study.

Other Name: Revlimid

Primary Outcome Measures :
  1. MTD [ Time Frame: Treatment duration up to 24 months ]
    the maximum tolerated dose (MTD) of lenalidomide

Secondary Outcome Measures :
  1. Dose Extension [ Time Frame: Treatment duration up to 24 months ]
    the recommended dose extension; subsequent to the maximum tolerated dose (MTD) of lenalidomide

Other Outcome Measures:
  1. EQ-5D-5L [ Time Frame: Treatment duration up to 24 months ]
    A self-reported descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems (1), slight problems(2), moderate problems(3), severe problems(4) and extreme problems(5). The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The new version can define 3,125 (=55) different health states. The five figure score represents a 1-5 score in each of 5 domains; the lower the score in each domain the less severe the problems in that domain.

  2. Inflammatory Neuropathy Cause and Treatment (INCAT) disability score [ Time Frame: Treatment duration up to 24 months ]
    The INCAT (Inflammatory Neuropathy Cause and Treatment) disability score is a measure of activity limitation. It is used frequently as a primary endpoint in inflammatory polyneuropathy clinical trials. The INCAT disability score combines arm and leg disability in a total score ranging from 0 (no signs of disability) to 12 (most severe disability score). It provides a good functional description of the arms and legs in a checklist form suitable for interviewing patients.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • • Patients must have an Anti-Myelin Associated Glycoprotein titer

    • Patients must have Distal acquired demyelinating sensorimotor (DADS) peripheral neuropathy phenotype as defined per European Federation of Neurological Societies (EFNS) demyelinating criteria with preferential distal nerve involvement, as captured per terminal latency index [terminal distance/(conduction velocity x terminal latency)], in the setting of a monoclonal gammopathy
    • Patients must be at least 18 years of age with no evidence of multiple myeloma, light chain amyloidosis or other hematologic disorder requiring treatment.
    • Patient may be enrolled at any time from last line of therapy.
    • Patients must have ANC > 1000/µL and Platelets ≥75,000/µL
    • Patients must have adequate hepatic function as evidenced by: total bilirubin < 1.5 mg/dL, alkaline phosphatase < 3X the ULN, and AST/ALT < 2X the ULN.
    • Patients must be able to take any of the following once lenalidomide starts and for at least 5 days after last dose lenalidomide: 1) 81-325 mg of coated aspirin daily; 2) full dose warfarin (target INR 2-3); 3) 2.5 mg or above of apixaban twice daily; 4) low molecular weight heparin; 5) 20 mg or above of rivaroxaban daily.
    • Patients must have adequate renal function as evidenced by serum creatinine < 2mg/dL or calculated creatinine clearance of ≥ 40ml/min within 14 days of registration using MDRD formula.
    • Patient must be able to swallow capsule or tablet.
    • Patients must provide informed consent.
    • All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
    • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
    • Two negative pregnancy tests will be required for all women of child bearing potential, with the second negative test having been at least 7 days prior to starting the study drug. Breast feeding is not permitted.
    • Fertility requirements

      • Female patients with child bearing potential must have two negative pregnancy tests, with the second negative test having been at least 7 days prior to starting the study drug.
      • Male patients must agree to use an adequate method of contraception starting from screening to 90 days after stopping the drug.
      • Female patients must be either posy-menopausal, free from menses ≥2 yrs., surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from sexual activity starting from screening to 90 days after stopping the drug.
      • Female patients of child bearing potential must agree to comply with the fertility and pregnancy test requirements dictated by the Rev-Assist program.

Exclusion Criteria:

  • • Patient with concurrent hematologic or oncologic malignancy requiring systemic treatment

    • History of allergic reaction (including erythema nodosum) to lenalidomide
    • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
    • Patients with a history of gastrointestinal surgery or other procedure that might, in the opinion of the investigator(s), interfere with the absorption or swallowing of the study drugs.
    • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff.
    • Any other medical condition, including mental illness or substance abuse deemed by the investigator(s) to likely interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03701711

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Contact: Julie Agriesti, MACPR, CCRC 614-685-5815

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United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Cassandra Fierro    734-232-0184   
Principal Investigator: Amro Stino, MD         
United States, Ohio
The Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: MacKenzie Kaschalk, BS    614-293-6953   
Sponsors and Collaborators
Ohio State University
Celgene Corporation
University of Michigan
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Principal Investigator: Bakri Elsheikh, MBBS Ohio State University
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Responsible Party: Bakri Elsheikh, Professor of Neurology, Ohio State University Identifier: NCT03701711    
Other Study ID Numbers: 2018H0150
First Posted: October 10, 2018    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Bakri Elsheikh, Ohio State University:
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents