, Jan. 30, 2014 /PRNewswire/ -- Cell Therapeutics, Inc. (CTI) (NASDAQ and MTA: CTIC) today announced the initiation of an international cooperative group Phase 2 clinical trial of pacritinib in adult patients with relapsed acute myeloid leukemia (AML) with mutations of the FLT3 gene. Mutation of the FLT3 gene is found in approximately one-third of AML patients and is an independent risk factor for poor prognosis. Pacritinib is an oral JAK2/FLT3 inhibitor that has demonstrated encouraging activity in preclinical models of AML with mutated FLT3 gene, including additional FLT3 mutations that confer resistance to other targeted FLT3 agents. The trial is being conducted by the AML Working Group of the National Cancer Research Institute Haematological Oncology Study Group in Acute Myeloid Leukemia (AML) and high risk Myelodysplastic Syndrome (MDS) under the sponsorship of
University and supported by Cancer Research UK. The trial management group is lead by Professor
Alan K. Burnett
, Head of Haematology in the Department of Medical Genetics, Haematology and Pathology at the School of Medicine at
"Mutation of the FLT3 gene in AML is associated with a high relapse rate and a poor prognosis with standard therapy; therefore, novel agents capable of inhibiting the activation of this gene are of great interest in the AML field," said Professor Burnett. "Pacritinib is a specific, potent inhibitor of the common FLT3 mutation and certain other generally drug resistant mutations. Because pacritinib also inhibits JAK2, which is independently associated with resistance to FLT3 inhibition and a poor prognosis in AML, this is an attractive agent to test in patients with relapsed FLT3 mutated AML who have limited options for beneficial therapy."
This Phase 2 trial is part of a larger ongoing study in AML, referred to as the AML17 trial, which includes multiple arms evaluating first line regimens for AML. Patients with the FLT3 mutation, who are enrolled in this study and relapse following standard therapy, will be offered therapy with pacritinib. Approximately 80 patients at sites in
will be enrolled and, if an encouraging response rate is observed, a pacritinib arm may be adopted in the first line therapy study.
About Acute Myeloid Leukemia
Although AML can occur at any age, adults aged 60 years and older are more likely to develop the disease than younger people. AML is a cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML may develop from the progression of other diseases, such as MDS, a blood cancer that also affects the bone marrow leading to a decrease in circulating red blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. Internal tandem duplication mutations of the FLT3 gene are found in approximately one-third of those diagnosed with AML.
The mutation is associated with an inferior outcome attributed to a higher relapse rate. The symptoms of AML are caused by the replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets and normal white blood cells, leading to infections and bleeding. AML progresses rapidly and is typically fatal within weeks or months if left untreated. Although a substantial proportion of younger individuals who develop AML can be cured, AML in the elderly typically responds poorly to standard therapy with few complete remissions.
Pacritinib is an oral tyrosine kinase inhibitor with dual activity against JAK2 and FLT3. 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.