Date: 2014-12-09
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition held December 6-9 in San Francisco, CA.
Company: CTI BioPharma - previously known as Cell Therapeutics (USA - WA)
Product: pacritinib
Action mechanism: tyrosine kinase inhbitor. Pacritinib is a next generation oral multikinase inhibitor with activity against JAK2 and FLT3, as well as other kinases. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. Pacritinib may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors. In November 2013, CTI and Baxter entered into a worldwide license agreement to develop and commercialize pacritinib. Under this agreement, CTI and Baxter will jointly commercialize pacritinib in the U.S., while Baxter has exclusive commercialization rights for all indications outside the U.S.
Disease: acute myeloid leukemia
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest news: * On December 9, 2014, CTI BioPharma announced data showing treatment with pacritinib, an investigational oral multikinase inhibitor in Phase 3 clinical development, preferentially killed acute myeloid leukemia (AML) cells with FLT3 mutations, overcame stromal protection and suppressed leukemic outgrowth from stroma adherent AML cells in both medium-term (7-14 days) and long-term (5-6 weeks) assays. The findings from this study were presented by Dr. Ceri Marrin, Consultant Haematologist, University Hospital of Wales at Cardiff University, during an oral presentation at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition held December 6-9 in San Francisco, CA. \" The efficacy of pacritinib was assessed in 62 primary AML samples that either carried a mutation in FLT3 (FLT3-ITD) or had wild type FLT3. A MS5 stromal co-culture model was used to assess FLT3-ITD cells that are adherent to non-adherent to stroma. The results showed that FLT3-ITD cells were more sensitive to pacritinib treatment compared to wild type samples and retained sensitivity to pacritnib treatment after seven days of co-culture with MS5 stroma cells. Following seven days of treatment, stroma-adherent FLT3-ITD cells had sustained suppression of leukemic outgrowth at 14 days. To assess long-term suppression of growth, the CD34+38- FLT3-ITD subpopulation of cells, which have in vivo engrafting ability, a leukemic stem cell property, and correlate with risk of clinical relapse, were plated with MS5 stroma cells. Pacritinib treatment significantly reduced cobblestone area forming cell (CAFC) frequency at five weeks. Leukemic cell signaling was measured by culturing FLT3-ITD cells on stroma in the presence of pacritinib for up to 24 hours. Activity of the p-STAT5, JAK2, AKT and ERK signaling pathways was assessed by immunoblot and luminescent assays. The authors concluded that pacritinib has the potential to overcome environmentally mediated drug resistance in FLT3 positive AML and demonstrated good synergy with cytarabine and a MEK inhibitor. A Phase 2 trial in patients with relapsed AML and FLT3 mutations is currently underway and a first-line study in elderly patients with AML is expected to be initiated in the near future
