Demyelinating Sensorimotor NeuropathyPhase 1NCT03701711
Lenalidomide in Anti-MAG Neuropathy: Phase 1b Study
A Phase 1 study testing Lenalidomide in people with Demyelinating Sensorimotor Neuropathy, run by Ohio State University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Demyelinating Sensorimotor Neuropathy
- What is being tested?
- Lenalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Sep 2018to 28 Feb 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • 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.
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- 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.
Who cannot join
- • 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan
Ann Arbor, Michigan, 48109
The Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Phase I Study of Lenalidomide in Combination with Dexamethasone in Anti-MAG Demyelinating Sensorimotor Neuropathy
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.
Read the detailed description
Primary Objective
- To determine the maximum tolerated dose (MTD) in phase I of lenalidomide and recommended dose in an extension cohort of lenalidomide of anti-MAG patients
- To examine the safety profile of lenalidomide in anti-MAG patients Secondary Objective To explore preliminary efficacy by using preselected, specifically tailored outcome measures that encompass quality of life, neurologic function, serum protein levels, and focused measures of proprioception
Study Design Part 1: 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.
To find the MTD and select the dose level for each cohort enrolled, we will use the Bayesian optimal interval design (BOIN).3-4 BOIN is implemented in a way that is similar to the traditional 3+3 design but has superior operating characteristics that are comparable to much more complex model-based designs, like the continual reassessment method (CRM).
The target toxicity rate will be 0.3 and the maximum sample size will be 12 patients. The BOIN design does not require a fixed cohort size throughout the trial. Thus, we will initially enroll in cohorts of size 1 but can modify subsequent cohort sizes as desired.
After the enrollment of the maximum sample size, the MTD will be selected using isotonic regression. The MTD will be the dose with the estimated toxicity rate closest to the target rate of 0.3.
Part 2: 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.
Patients who have not had disease progression, have experienced acceptable toxicity or have not withdrawn for any other reason after 24 months will be eligible to continue protocol treatment at their current dose level until disease progression, unacceptable toxicity, or refusal. Those patients who have not progressed and who have experienced unacceptable toxicity may be eligible for re-treatment at a lower dose. A maximum of 2 reductions are allowed.
Criteria for discontinuation of protocol therapy include:
- Request by the patient to withdraw
- Unacceptable adverse events
- Treatment delay of >4weeks
- Intercurrent illness which would, in the judgment of the investigator, affect assessments of clinical status to a significant degree that require discontinuation of drug
- Non-protocol chemotherapy, or an experimental drug during the trial
Patients who discontinue treatment for any of the above reasons will go to event monitoring. Once a patient has entered the event monitoring phase of the trial, his/her therapy is at the discretion of the treating physician. Patients' charts will be reviewed for progression and survival endpoints during visits with treating physicians.
Peripheral blood (10ml purple top EDTA for immediate analysis and 6ml red top for possible later cytokine evaluation) will be collected at pre-treatment and after cycles 1,2,3,6,9,12, as well as 18 and 24 (for extension phase) for immunome correlative studies.
- Conditions
- Demyelinating Sensorimotor Neuropathy
- Being tested
- Lenalidomide
- Keywords
- Lenalidomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Also called Revlimid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD
the maximum tolerated dose (MTD) of lenalidomide
Measured: Treatment duration up to 24 months
Secondary outcomes (1)
Dose Extension
the recommended dose extension; subsequent to the maximum tolerated dose (MTD) of lenalidomide
Measured: Treatment duration up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2018
- Study start10 Sep 2018
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Why it stopped: Higher than expected occurrence of VTE (venous thromboembolic event)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Demyelinating Sensorimotor NeuropathyStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm dose escalation study
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation, University of Michigan
- Responsible party
- Principal investigator, Bakri Elsheikh, Ohio State University
- Investigators
- Bakri Elsheikh, MBBS, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03701711
- Sponsor's protocol ID
- 2018H0150
- Status last verified
- Mar 2023
- First submitted
- 8 Oct 2018
- Last updated
- 27 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 38015467
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Lenalidomide in Combination with Dexamethasone in Anti-MAG Demyelinating Sensorimotor Neuropathy
- ClinicalTrials.gov ID
- NCT03701711
- Acronym / sponsor ID
- 2018H0150
- Conditions
- Demyelinating Sensorimotor Neuropathy
- Keywords
- Lenalidomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Higher than expected occurrence of VTE (venous thromboembolic event)
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Collaborators
- Celgene Corporation, University of Michigan
- Study start
- 10 Sep 2018 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 10 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary Objective
- To determine the maximum tolerated dose (MTD) in phase I of lenalidomide and recommended dose in an extension cohort of lenalidomide of anti-MAG patients
- To examine the safety profile of lenalidomide in anti-MAG patients Secondary Objective To explore preliminary efficacy by using preselected, specifically tailored outcome measures that encompass quality of life, neurologic function, serum protein levels, and focused measures of proprioception
Study Design Part 1: 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.
To find the MTD and select the dose level for each cohort enrolled, we will use the Bayesian optimal interval design (BOIN).3-4 BOIN is implemented in a way that is similar to the traditional 3+3 design but has superior operating characteristics that are comparable to much more complex model-based designs, like the continual reassessment method (CRM).
The target toxicity rate will be 0.3 and the maximum sample size will be 12 patients. The BOIN design does not require a fixed cohort size throughout the trial. Thus, we will initially enroll in cohorts of size 1 but can modify subsequent cohort sizes as desired.
After the enrollment of the maximum sample size, the MTD will be selected using isotonic regression. The MTD will be the dose with the estimated toxicity rate closest to the target rate of 0.3.
Part 2: 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.
Patients who have not had disease progression, have experienced acceptable toxicity or have not withdrawn for any other reason after 24 months will be eligible to continue protocol treatment at their current dose level until disease progression, unacceptable toxicity, or refusal. Those patients who have not progressed and who have experienced unacceptable toxicity may be eligible for re-treatment at a lower dose. A maximum of 2 reductions are allowed.
Criteria for discontinuation of protocol therapy include:
- Request by the patient to withdraw
- Unacceptable adverse events
- Treatment delay of >4weeks
- Intercurrent illness which would, in the judgment of the investigator, affect assessments of clinical status to a significant degree that require discontinuation of drug
- Non-protocol chemotherapy, or an experimental drug during the trial
Patients who discontinue treatment for any of the above reasons will go to event monitoring. Once a patient has entered the event monitoring phase of the trial, his/her therapy is at the discretion of the treating physician. Patients' charts will be reviewed for progression and survival endpoints during visits with treating physicians.
Peripheral blood (10ml purple top EDTA for immediate analysis and 6ml red top for possible later cytokine evaluation) will be collected at pre-treatment and after cycles 1,2,3,6,9,12, as well as 18 and 24 (for extension phase) for immunome correlative studies.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm dose escalation study
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide escalation and expansion | Experimental | Drug: LenalidomideAmong 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- • Patients must have an Anti-Myelin Associated Glycoprotein titer
Key exclusion criteria (6 listed)
- • Patient with concurrent hematologic or oncologic malignancy requiring systemic treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenalidomideAlso: RevlimidDose 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. | Drug | Lenalidomide escalation and expansion |
Primary outcome
MTD
Time frame: Treatment duration up to 24 months
the maximum tolerated dose (MTD) of lenalidomide
1 secondary outcome
Dose Extension
Time frame: Treatment duration up to 24 months
Results and safety
The study was stopped early (reason given: Higher than expected occurrence of VTE (venous thromboembolic event)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2024.
- Derived from this study: PubMed 38015467Stino 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bakri Elsheikh, MBBS principal investigator
Ohio State University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenalidomide in people with Demyelinating Sensorimotor Neuropathy, run by Ohio State University at 2 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 18 inclusion and 6 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 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Higher than expected occurrence of VTE (venous thromboembolic event)). Results are not available in the source record.
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?
MTD (time frame: Treatment duration up to 24 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 NCT03701711, which also lists 1 linked publication.
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 27 Sep 2024; AzTrials last refreshed its copy on 31 Oct 2026.