Date: 2014-04-15
Type of information: Initiation of the trial
phase: 1
Announcement: initiation of the trial
Company: Karyopharm Therapeutics (USA - MA)
Product: selinexor (KPT-330 - (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-N'-(pyrazin-2-yl)acrylohydrazide) and Dacogen®(decitabine)
Action
mechanism: selective inhibitor of nuclear export/nucleoside analogue. Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding to the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus, which subsequently reinitiates and amplifies their tumor suppressor function. This is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 300 patients have been treated with Selinexor in Phase 1 and Phase 2 clinical trials in advanced hematologic malignancies and solid tumors. Additional Phase 1 and Phase 2 studies are ongoing or currently planned and three registration-directed clinical trials in hematological indications are expected to begin enrollment during 2014. Decitabine is a cytosine nucleoside analogue which inhibits DNA methyltransferase.
Disease: acute myeloid leukemia (AML)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This phase I trial studies the side effects and best dose of Selinexor when given together with decitabine in treating patients with acute myeloid leukemia that has returned after treatment (relapsed) or does not respond to treatment (refractory). In this combination study, patients with relapsed and/or refractory AML or newly diagnosed AML patients ?60 years of age ineligible for intensive chemotherapy will receive decitabine intravenously on days 1-10 and Selinexor orally twice weekly beginning on day 11 of each 31-day cycle. The primary goal of the study is to determine the maximum tolerated dose and the recommended Phase 2 dose of this combination in up to 42 patients. The secondary goal of the study is to determine the response rates and duration of leukemia control. (NCT02093403)
Latest
news: * On April 15, 2014, Karyopharm Therapeutics announced the initiation of a Phase 1 combination trial of selinexor (KPT-330) in combination with the DNA methylation inhibitor decitabine (Dacogen®) in patients with relapsed or refractory acute myeloid leukemia and in patients age ?60 years with newly diagnosed AML. The study is being conducted at The Ohio State University Comprehensive Cancer Center under the direction of principal investigator Ramiro Garzon, MD, Associate Professor.
