Ricolinostat (ACY-1215)
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General information
Class/mechanism: Selective HDAC6 inhibitor. Histone deacetylase (HDAC) inhibitors result in hyperacetylation of histones and modulate 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
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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
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
- 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
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