Clinical trial NCT01816620: Study to Evaluate Lenalidomide Plus Dexamethasone in Patients With Newly Diagnosed POEMS Syndrome
Official title: An Open-label Phase II Study to Determine the Efficacy and Safety of Lenalidomide Plus Dexamethasone (LDex) in Patients With Newly Diagnosed POEMS Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: POEMS Syndrome
Keywords: POEMS Syndrome
lenalidomide
newly diagnosed
plasma cell disorder
Dexamethasone
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2013-03-22
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients must understand and voluntarily sign an informed consent form.
2. Older than 18 years old at the time of signing consent.
3. Meet the diagnostic criteria of POEM syndrome.
4. Must be cytotoxic treatment naive. However, previous or existing corticosteroid (prednisone or dexamethasone) or intravenous immunoglobin (IVIG) therapy is allowed.
5. 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.
6. Male subjects must agree to use condoms throughout study drug therapy.

Exclusion Criteria:

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
2. Pregnant or lactating females.
3. 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.
4. 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.
5. Known hypersensitivity or prior history of uncontrollable side effects to dexamethasone therapy.
6. Prior use of cytotoxic drugs.
7. Subjects who are unable or unwilling to undergo antithrombotic therapy.

Primary outcomes:
measure: Hematological response rate
timeFrame: last day of the LDx treatment regimen (up to 9 months)
measure: Neurological response rate defined by ONLS score
timeFrame: last day of the LDx treatment regimen (up to 9 months)
Secondary outcomes:
measure: response rate of critical organs
timeFrame: every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months
measure: Response rate of serum vascular endothelial growth factor (VEGF) level
timeFrame: every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months
measure: Time to initial neurological response
timeFrame: every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months
measure: Overall survival
timeFrame: 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)
measure: Relapse free survival
timeFrame: 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)
measure: adverse events
timeFrame: throughout the treatment and until 30 days after the administration of the last dose of a study drug
measure: time to the best neurological response
timeFrame: every month during the first 3 months calculated from the day study started, then every 3 months in the next 9 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Jian Li, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking Union Medical College Hospital
name: Dao-bin Zhou, MD
role: STUDY_DIRECTOR
References:
citation: Gao Y, Zhang S, Yang L, Li J, Liu Y, Wang T. Skin Responses in Newly Diagnosed Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome After Therapy With Low-Dose Lenalidomide Plus Dexamethasone. Front Immunol. 2021 May 6;12:681360. doi: 10.3389/fimmu.2021.681360. eCollection 2021.
citation: Liu LS, Zhang X, Zhao H, Gao XM, Zhou DB, Dai RP, Li J. Reliability of optic disc edema area in estimating the severity of papilledema in patients with POEMS syndrome. Orphanet J Rare Dis. 2020 May 19;15(1):116. doi: 10.1186/s13023-020-01392-x.
citation: Li J, Huang XF, Cai QQ, Wang C, Cai H, Zhao H, Zhang L, Cao XX, Gale RP, Zhou DB. A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Am J Hematol. 2018 Jun;93(6):803-809. doi: 10.1002/ajh.25100. Epub 2018 Apr 18.