Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial

Abstract

IntroductionPolyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a fatal systemic disorder associated with plasma cell dyscrasia and the overproduction of the vascular endothelial growth factor (VEGF). Recently, the prognosis of POEMS was substantially improved by introduction of therapeutic intervention for myeloma. However, no randomised clinical trial has been performed because of the rarity and severity of the disease.Methods and analysisThe Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome, with an additional 48-week open-label safety study. Adults with POEMS syndrome who have no indication for transplantation are assessed for eligibility at 12 tertiary neurology centres in Japan. Patients who satisfy the eligibility criteria are randomised (1:1) to receive thalidomide (100–300 mg daily) plus dexamethasone (12 mg/m2 on days 1–4 of a 28-day cycle) or placebo plus dexamethasone. Both treatments were administered for 24 weeks (six cycles; randomised comparative study period). Patients who complete the randomised study period or show subacute deterioration during the randomised period participate in the subsequent 48-week open-label safety study (long-term safety period). The primary end point of the study is the reduction rate of serum VEGF levels at 24 weeks.Ethics and disseminationThe protocol was approved by the Institutional Review Board of each hospital. The trial was notified and registered at the Pharmaceutical and Medical Devices Agency, Japan (No. 22-1716). The J-POST Trial is currently ongoing and is due to finish in August 2015. The findings of this trial will be disseminated through peer-reviewed publications and conference presentations and will also be disseminated to participants.Trial registration numberUMIN000004179 and JMA-IIA00046.

Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study

“… 13 While the adequacy of serum VEGF as a surrogate endpoint needs further confirmation, this marker may facilitate prospective clinical trials on the safety and efficacy of these newer drugs despite the rarity of this syndrome. In fact, we are now conducting a multicentre, double-blind and randomised controlled clinical trial 29 to evaluate the efficacy and safety of thalidomide for POEMS syndrome using the rate of VEGF decrease over 6 months post treatment as the primary endpoint (declared and registered to the Japan Pharmaceuticals and Medical Devices Agency).…”

POEMS syndrome: Update on diagnosis, risk‐stratification, and management

“…Enthusiasm for this therapy should be tempered by the risk of peripheral neuropathy induced by this drug. The Japanese reaccruing to a randomized trial of thalidomide plus dexamethasone versus dexamethasone alone [180].…”

Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan

“…Since the 1990s the treatment strategy for POEMS syndrome has shifted to suppressing underlying monoclonal plasma cell proliferation using therapeutic interventions developed for multiple myeloma. A favorable prognosis has been reported after autologous stem cell transplantation (ASCT) after melphalan-based highdose chemotherapy, and novel agents for multiple myeloma such as proteasome inhibitors and immunomodulatory drugs significantly improved the prognosis of POEMS syndrome [11][12][13][14][15][16][17][18]. ASCT has been reported as a promising treatment procedure in patients younger than 65 years; however, the information about its safety and long-term outcomes is limited because of the rarity of the disease [19][20][21][22][23][24][25][26][27].…”