Ignite Creation Date:
2024-05-06 @ 12:12 PM
Last Modification Date:
2024-10-26 @ 12:55 PM
Study NCT ID:
NCT03701711
Status:
TERMINATED
Last Update Posted:
2023-10-24
First Post:
2018-10-08
Brief Title:
Lenalidomide in Anti-MAG Neuropathy Phase 1b Study
Sponsor:
Ohio State University
Organization:
Ohio State University
Study Overview
Official Title:
A Phase I Study of Lenalidomide in Combination with Dexamethasone in Anti-MAG Demyelinating Sensorimotor Neuropathy
Status:
TERMINATED
Status Verified Date:
2023-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Higher than expected occurrence of VTE venous thromboembolic event
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 findingsThe 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 20mgday 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
1 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
2 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 1815 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 BOIN3-4 BOIN is implemented in a way that is similar to the traditional 33 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 03 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 03
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 hisher 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 1236912 as well as 18 and 24 for extension phase for immunome correlative studies
1 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
2 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 1815 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 BOIN3-4 BOIN is implemented in a way that is similar to the traditional 33 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 03 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 03
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 hisher 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 1236912 as well as 18 and 24 for extension phase for immunome correlative studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None