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

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

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

Study Overview

• Status: Completed
• Conditions: POEMS Syndrome
• Intervention / Treatment: Drug: Lenalidomide, Dexamethasone

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lenalidomide, dexamethasone; Lenalidomide 10mg qd d1-21 & dexamethasone 40mg qw d1,8,15,22

Drug: Lenalidomide, Dexamethasone; 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.; Other Names: Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Celgene Corporation
• Investigators: Principal Investigator: Jian li, M.D., Peking Union Medical College Hospital; Study Director: Dao-bin Zhou, MD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: March 14, 2013
• First Submitted That Met QC Criteria: March 21, 2013
• First Posted (Estimate): March 22, 2013

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 23, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: lenalidomide; Dexamethasone; newly diagnosed; POEMS Syndrome; plasma cell disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Immunoproliferative Disorders; Disease; Congenital Abnormalities; Hematologic Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Paraproteinemias; Blood Protein Disorders; Abnormalities, Multiple; Polyneuropathies; Syndrome; POEMS Syndrome; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: POEMS-01