Ricolinostat (ACY-1215)
General information
Class/mechanism: Selective HDAC6 inhibitor. Histone deacetylase (HDAC) inhibitors result in hyperacetylation of histones and modulates gene expression by creating an open chromatin state that leads to expression of previously silenced genes. This modulation may result in decreased expression of oncogenes, induction of cell cycle arrest, promotion of apoptosis, and decreased invasion of tumor cells. It is hypothesized that selectively inhibiting HDAC6 rather than additional members of the HDAC family may be able to maintain efficacy while resulting in fewer side effects associated with pan-HDAC inhibitors, such as myelosuppression, fatigue, nausea, vomiting, and diarrhea.[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.
Diseases for which it is used
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
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 40 mg PO once per week
- Ricolinostat (ACY-1215, Rocilinostat) 160 mg PO BID once per day on days 1 to 21
28-day cycles
References
- 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, Raje et al. 2012
Different doses & schedule of Rocilinostat were used at different points in this Phase I/II Study. Please refer to Raje et al. 2012 regarding the various doses of Rocilinostat used in the monotherapy part.
- Bortezomib (Velcade) 1.0 mg/m2 (route not specified) once per day on days 1, 4, 8, 11
- Dexamethasone (Decadron) 20 mg PO once per day on days 1, 2, 4, 5, 8, 9, 11, 12
- Ricolinostat (ACY-1215, Rocilinostat) 40 mg PO (40 mg was the "starting dose." Schedule was not clearly specified; during the monotherapy "Part 1" of the study, it was given on days 1 to 5 and days 8 to 12)
21-day cycles x "up to 6 cycles of therapy, or more if experiencing clinical benefit"
References
- 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
Also known as
ACY-1215, Rocilinostat
References
- ↑ Ricolinostat in Multiple Myeloma, Acetylon Pharmaceuticals
- ↑ 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
- ↑ 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