Cell Therapeutics, Inc. (CTI) has 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 Cardiff 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 Cardiff University.
"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.
Professor Burnett continued, "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 England and Wales will be enrolled and, if an encouraging response rate is observed, a pacritinib arm may be adopted in the first line therapy study.