In Brief: Phase III Trials in Multiple Myeloma

October 19, 2013
Special Reports, B-Cell Malignancies, Volume 1, Issue 1

Phase III trials in multiple myeloma, including plitidepsin, elotuzumab, carfilzomib, masitinib, and panobinostat.

  • Plitidepsin(Aplidin; PharmaMar, SA), which induces cell death through various cellular pathways, was originally isolated from a marine organism known as a sea squirt.1A randomized, multicenter, open-label, phase III study of plitidepsin in combination with dexamethasone vs dexamethasone alone in patients with relapsed/refractory multiple myeloma is currently recruiting participants.2

  • Elotuzumab(HuLuc63; Bristol-Myers Squibb (BMS), AbbVie) is a humanized monoclonal antibody that binds to the cell surface glycoprotein CA1. The cell surface protein is found primarily on myeloma cells (not on normal bone marrow cells).3A phase III study of lenalidomide and dexamethasone with or without elotuzumab to treat newly diagnosed, previously untreated multiple myeloma (ELOQUENT 1) is currently recruiting participants.4
  • A phase III study of lenalidomide and dexamethasone with or without elotuzumab to treat relapsed or refractory multiple myeloma (ELOQUENT-2) is ongoing but not recruiting participants.5

  • Carfilzomib(Kyprolis; Onyx Therapeutics) is a selective proteasome inhibitor.6A phase III study with carfilzomab and dexamethason versus Velcade and dexamethasone for relapsed multiple myeloma patients (ENDEAVOR) is currently recruiting participants.7
  • A phase III study of carfilzomib, melphalan, prednisone vs bortezomib, melphalan, prednisone in newly diagnosed multiple myeloma (CLARION) is currently recruiting participants.8

  • Masitinib(AB1010; AB Science) is a protein kinase inhibitor.9A phase III study to evaluate the efficacy and safety of masitinib in patients with relapsed or refractory multiple myeloma is currently recruiting participants.10

  • Panobinostat(LBH589; Novartis) is a highly potent pan-deacetylase inhibitor (pan-DACi), (inclusive of HDAC6) that disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates, and triggers myeloma cell death.11A multicenter, randomized, double-blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma is ongoing (not recruiting).12

References

  1. Munoz-Alonso, Gonzalex-Santiago L, Martinez T, et al. The mechanism of action of plitidepsin. Curr Opin Drugs. 2009;10:536-542. http://www.ncbi.nlm.nih.gov/pubmed/19513942
  2. Clinicaltrials.gov. Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE). Available at: http://clinicaltrials.gov/show/NCT01102426
  3. National Cancer Institute (NCI). Elotuzumab. Available at: http://www.cancer.gov/drugdictionary?cdrid=532249
  4. Clinicaltrials.gov. Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma (ELOQUENT-1). Available at: http://clinicaltrials.gov/ct2/show/NCT01335399?term=elotuzumab&rank=8 Millennium: The Takeda Oncology Company. Newsroom. Available at: http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1826370&highlight=
  5. Clinicaltrials.gov. Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT - 2). Available at: http://clinicaltrials.gov/show/NCT01239797
  6. National Cancer Institute (NCI). Carfilzomib. Available at: http://www.cancer.gov/drugdictionary?CdrID=459751
  7. Clincaltrials.gov. Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR). Available at: http://clinicaltrials.gov/ct2/show/NCT01568866?term=carfilzomib+and+multiple+myeloma&rank=5
  8. Clinicaltrials.gov. Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (CLARION). Available at: http://clinicaltrials.gov/ct2/show/NCT01818752?term=CLARION&rank=1
  9. National Cancer Institute (NCI). Masitinib mesylate. Available at: http://www.cancer.gov/drugdictionary?CdrID=629109
  10. Clinicaltrials.gov. A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Patients With Relapse or Refractory Multiple Myeloma. Available at: http://clinicaltrials.gov/ct2/show/NCT01470131?term=masitinib+and+multiple+myeloma&rank=1
  11. National Cancer Institute (NCI). Panobinostat. Available at: http://www.cancer.gov/drugdictionary?cdrid=530790
  12. Clinicaltrials.gov. Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1). Available at: http://clinicaltrials.gov/ct2/show/NCT01023308?term=PANORAMA+I+and+multiple+myeloma&rank