Date: 2014-04-21
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)
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.
Disease: relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML
Therapeutic area: Cancer - Oncology
Country:
Trial
details: This research study involves participants who have acute lymphoblastic or acute myelogenous leukemia that has relapsed or has become resistant (or refractory) to standard therapies. This research study is evaluating a drug called KPT-330. Laboratory and other studies suggest that the study drug, KPT-330, may prevent leukemia cells from growing and may lead to the destruction of leukemia cells. It is thought that KPT-330 activates cellular processes that increase the death of leukemia cells. The main goal of this study is to evaluate the side effects of KPT-330 when it is administered to children and adolescents with relapsed or refractory leukemia. (NCT02091245)
Latest
news: * On April 21, 2014, Karyopharm Therapeutics announced the initiation of its first pediatric clinical study, a Phase 1 trial of selinexor (KPT-330) in pediatric patients. The trial will enroll up to 28 children with relapsed or refractory acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). The study is being led by Dana-Farber/Boston Children's Cancer and Blood Disorders Center under the direction of principal investigator Andrew Place, MD, PhD, Associate Director of Developmental Therapeutics, and has been partially funded by a grant from the William Lawrence & Blanche Hughes Foundation. Preclinical results from Dr. Julia Etchin in Dr. Thomas Look's laboratory at Dana-Farber Cancer Institute (DFCI), as well as other laboratories, have shown that selinexor has potent anti-AML and anti-ALL activity in vitro and in vivo. This activity is associated with enhancement of nuclear levels of tumor suppressor proteins, leading to the selective apoptosis of neoplastic cells. In addition, Dr. Look and colleagues have shown that selinexor can kill leukemia stem cells, which are highly resistant to standard anti-leukemia treatments in vitro and in animal models. Oral selinexor has shown single agent anti-leukemic activity in adult patients with heavily pretreated, relapsed/refractory AML. Studies in adults with refractory ALL have also been initiated.
