Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study

NCT03701711 | Terminated Phase 1 FDA Drug

• 1 other identifier: 2018H0150
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

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.

Conditions

Demyelinating Sensorimotor Neuropathy

Keywords

Lenalidomide

Outcome Measures

Primary Outcomes (1)

• MTD

  the maximum tolerated dose (MTD) of lenalidomide

  Treatment duration up to 24 months

Secondary Outcomes (1)

• Dose Extension

  Treatment duration up to 24 months

Other Outcomes (2)

• EQ-5D-5L

  Treatment duration up to 24 months

• Inflammatory Neuropathy Cause and Treatment (INCAT) disability score

  Treatment duration up to 24 months

Study Arms (1)

Lenalidomide escalation and expansion

EXPERIMENTAL

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

Interventions

Lenalidomide DRUG

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.

Also known as: Revlimid

Lenalidomide escalation and expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University: lead
• Celgene Corporation: collaborator
• University of Michigan: collaborator

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Stino AM, Bumma N, Smith R, Davalos L, Allen J, Ye JC, Pianko M, Campagnaro E, Fierro C, Awad A, Murdock B, Pietrzak M, Loszanski G, Kline DM, Efebera Y, Elsheikh B. Lenalidomide in the treatment of anti-myelin-associated glycoprotein neuropathy: A phase 1 study to identify the maximum tolerated dose. Eur J Neurol. 2024 Mar;31(3):e16164. doi: 10.1111/ene.16164. Epub 2023 Nov 28.

  PMID: 38015467 DERIVED

MeSH Terms

Interventions

Lenalidomide

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Bakri Elsheikh, MBBS

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Model Details: Single arm dose escalation study

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 10, 2018
• Study Start: September 10, 2018
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: September 27, 2024

Record last verified: 2023-03

Locations

US (2)