Ricolinostat (ACY-1215, Rocilinostat)

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General information

Class/mechanism from the NCI Drug Dictionary: An orally bioavailable, specific inhibitor of histone deacetylase 6 (HDAC6) with potential antineoplastic activity. Ricolinostat selectively targets and binds to HDAC6, thereby disrupting the Hsp90 protein chaperone system through hyperacetylation of Hsp90 and preventing the subsequent aggresomal protein degradation. This leads to an accumulation of unfolded and misfolded ubiquitinated proteins and may eventually induce cancer cell apoptosis, and inhibition of cancer cell growth.[1][2][3]
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Preliminary data

Multiple myeloma

Lenalidomide, Dexamethasone, Ricolinostat

Regimen, Yee et al. 2014

Doses & schedule of Ricolinostat varied at different points in the study. The regimen below is based on "Part B" as described in Yee et al. 2014.

28-day cycles

References
  1. Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. link to abstract

Bortezomib, Dexamethasone, Rocilinostat

Regimen

Different doses & schedule of Rocilinostat were used at different points in this Phase I/II Study; this is the recommended Phase II dose used in the Cohort 4 Expansion.

  • Bortezomib (Velcade) as follows:
    • Cycles 1 to 5: 1.3 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
    • Cycle 6 onwards: 1.3 mg/m2 (route not specified) once per day on days 1 & 8
  • Dexamethasone (Decadron) as follows:
    • Cycles 1 to 5: 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
    • Cycle 6 onwards: 20 mg PO once per day on days 1, 2, 8, 9
  • Ricolinostat (ACY-1215, Rocilinostat) 160 mg PO once per day on days 1 to 5, 8 to 12

21-day cycles

References
  1. Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S. Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma. Clin Cancer Res. 2017 Jul 1;23(13):3307-3315. Epub 2017 Jan 4. link to original article PubMed

Also known as

  • Code name: ACY-1215
  • Generic name: rocilinostat

References

  1. Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals
  2. Andrew J Yee, MD, Peter M. Voorhees, MD, William Bensinger, Jesus G. Berdeja, MD, Jeffrey G Supko, PhD, Paul G. Richardson, David Tamang, PhD, Simon S Jones, PhD, Gretchen Patrick, Catherine Wheeler, MD and Noopur Raje, MD. Ricolinostat (ACY-1215), a Selective HDAC6 Inhibitor, in Combination with Lenalidomide and Dexamethasone: Results of a Phase 1b Trial in Relapsed and Relapsed Refractory Multiple Myeloma. 2014 ASH Annual Meeting abstract 4772. link to abstract
  3. Noopur Raje, MD, Parameswaran N Hari, MD, MRCP, MS, Dan T. Vogl, MD, MSCE, Sundar Jagannath, MD, Robert Z. Orlowski, M.D., Ph.D., Jeffrey G Supko, PhD, Patricia Stephenson, ScD, Simon S Jones8, Catherine Wheeler, MD and Sagar Lonial, MD. Rocilinostat (ACY-1215), a Selective HDAC6 Inhibitor, Alone and in Combination with Bortezomib in Multiple Myeloma: Preliminary Results From the First-in-Humans Phase I/II Study. 2012 ASH Annual Meeting abstract 4061. link to abstract