A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001)

Summary

The primary purpose of this study was to determine the recommended dose (RD) of birabresib (MK-8628) /OTX015 for further phase II studies, in participants with acute leukemia (AL) including acute myeloid leukemia (AML; de novo and secondary to a myelodysplastic syndrome) and acute lymphoblastic leukemia (ALL) or other hematologic malignancies (OHM) including diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM). The first phase of the study will be a dose escalation phase to determine the Phase II RD using dose-limiting toxicities (DLTs). Once the RD is determined, participants will be enrolled in an expansion phase at the RD to determine preliminary efficacy in AL and OHM cohorts. Participants received therapy in 21-day cycles until disease progression, intolerable toxicity, or treatment interruption for \>2 weeks due to toxicity.

Timeline

Start

2012-12-14

Primary completion

2017-01-20

Completion

2017-01-20

Publications

• Results Odore E, Lokiec F, Cvitkovic E, Bekradda M, Herait P, Bourdel F, Kahatt C, Raffoux E, Stathis A, Thieblemont C, Quesnel B, Cunningham D, Riveiro ME, Rezai K. Phase I Population Pharmacokinetic Assessment of the Oral Bromodomain Inhibitor OTX015 in Patients with Haematologic Malignancies. Clin Pharmacokinet. 2016 Mar;55(3):397-405. doi: 10.1007/s40262-015-0327-6.
• Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, Morschhauser F, Karlin L, Broussais F, Rezai K, Herait P, Kahatt C, Lokiec F, Salles G, Facon T, Palumbo A, Cunningham D, Zucca E, Thieblemont C. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e196-204. doi: 10.1016/S2352-3026(16)00021-1. Epub 2016 Mar 18.
• Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, Taussig DC, Rezai K, Roumier C, Herait P, Kahatt C, Quesnel B, Michallet M, Recher C, Lokiec F, Preudhomme C, Dombret H. Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e186-95. doi: 10.1016/S2352-3026(15)00247-1. Epub 2016 Mar 18.

Drugs

Indications