Study to Evaluate Lenalidomide Plus Dexamethasone in Patients With Newly Diagnosed POEMS Syndrome

Study Overview
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Brief Summary
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The purpose of this prospective study is to determine the efficacy and safety of lenalidomide plus dexamethasone in patients with newly diagnosed POEMS syndrome.

Detailed Description
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The investigators propose to use the adverse effects as well as the need for dose reduction as a criterion to judge tolerability of treatment. The primary endpoint would be hematological response rate according to international myeloma working group (IMWG) response criteria for amyloidosis and neurological response rate defined by overall neuropathy limitation scale (ONLS) score. This study expects to enroll approximately 41 subjects.

Official Title
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An Open-label Phase II Study to Determine the Efficacy and Safety of Lenalidomide Plus Dexamethasone (LDex) in Patients With Newly Diagnosed POEMS Syndrome

Conditions
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POEMS Syndrome

Intervention / Treatment
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* Drug: Lenalidomide, Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must understand and voluntarily sign an informed consent form. Older than 18 years old at the time of signing consent. Meet the diagnostic criteria of POEM syndrome. Must be cytotoxic treatment naive. However, previous or existing corticosteroid (prednisone or dexamethasone) or intravenous immunoglobin (IVIG) therapy is allowed. Women of childbearing potential must understand that the study medication could have a potential teratogenic risk. They should undergo complete contraception during the study period. Male subjects must agree to use condoms throughout study drug therapy. Exclusion Criteria: Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. Pregnant or lactating females. Any of the following laboratory abnormalities: Absolute neutrophil count(ANC) of<1.0×10E9 cell/L. Platelet count<50×10E9 cell/L. Renal failure requiring dialysis. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times of the normal upper limit. Prior history of malignancies, but not including basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and T1a or T1b prostate cancer. Known hypersensitivity or prior history of uncontrollable side effects to dexamethasone therapy. Prior use of cytotoxic drugs. Subjects who are unable or unwilling to undergo antithrombotic therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lenalidomide, dexamethasone<br>Lenalidomide 10mg qd d1-21 & dexamethasone 40mg qw d1,8,15,22 | Drug: Lenalidomide, Dexamethasone<br>* 12 cycles of lenalidomide and dexamethasone, each cycle lasts 28 days. For patients with Ccr equal to or higher than 30ml/min, oral lenalidomide 10mg once daily for days 1-21 out of a 28 cycle. For patients with Ccr lower than 30ml/min, oral lenalidomide 10mg once every other day for days 1-21 out of a 28 cycle. All the patients take Dexamethasone orally 40mg once weekly for day 1,8,15,22 out of a 28 cycle.<br>* Other names: Revlimid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological response rate |  | last day of the LDx treatment regimen (up to 9 months) | 
| Neurological response rate defined by ONLS score |  | last day of the LDx treatment regimen (up to 9 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| response rate of critical organs |  | every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months | 
| Response rate of serum vascular endothelial growth factor (VEGF) level |  | every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months | 
| Time to initial neurological response |  | every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months | 
| Overall survival |  | From date of first diagnosis until the date of death from any cause, otherwise patients will be censored in June, 2018 (up to 5 years) | 
| Relapse free survival |  | From date of first diagnosis until the date of first documented relapse or date of death from any cause, whichever came first, otherwise patients will be censored in June, 2018 (up to 5 years) | 
| adverse events |  | throughout the treatment and until 30 days after the administration of the last dose of a study drug | 
| time to the best neurological response |  | every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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POEMS Syndrome, lenalidomide, newly diagnosed, plasma cell disorder, Dexamethasone