US-based CTI BioPharma has announced the start of an international cooperative group Phase II clinical trial of tosedostat in combination with low-dose cytarabine in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS).
Sponsored by the UK's Cardiff University, the trial is being carried out by the National Cancer Research Institute Haematological Oncology Study Group and is led by professor Alan Burnett, head of haematology in the department of medical genetics, haematology and pathology at Cardiff University's School of Medicine.
Tosedostat is a first-in-class selective inhibitor of aminopeptidases, which are essential for tumour cells to provide amino acids needed for growth and tumour cell survival.
CTI BioPharma secured licence of tosedostat from Chroma Therapeutics, which is now facilitating drug supply for the trial.
Burnett said as the population of patients 65 years of age and older with AML continues to grow, there are a large number of patients who are not suitable for conventional intensive chemotherapy.
"New agents that are being developed to target the underlying biology of the disease, such as tosedostat, may provide hope for these patients where there has been very little improvement in the outcome of these patients over the last couple of decades," Burnett said.
"Tosedostat has demonstrated encouraging clinical activity in AML with manageable toxicities that can be administered primarily as out-patient therapy, and we are pleased to get this study underway."
In this Phase II/III trial, which is referred to as the AML less intensive (LI-1) trial, patients will be randomised to standard treatment, low dose cytarabine, versus one of five novel investigational treatments, with one tosedostat, each in combination with low dose cytarabine.
The trial will use a 'Pick a Winner' trial design, under which the Phase II portion of the study is expected to initially enrol 50 patients per arm. If the complete response rate of cytarabine plus novel therapy is satisfactory, an additional 50 patients for each arm would be enrolled in this portion.
Based on an interim analysis of complete response results, the trial management group may decide to move the applicable trial into the Phase III portion, which would then undertake to enrol about 100 additional patients.
The company said that overall survival (OS) will serve as the primary endpoint of the trial.
Tosedostat has shown anti-tumour responses in blood-related cancers and solid tumours in Phase I/II clinical trials.
The company has an exclusive marketing and co-development agreement with Chroma Therapeutics for drug candidate tosedostat in North, Central and South America.
Image: Bone marrow aspirate showing acute myeloid leukemia. Arrows indicate Auer rods. Photo: courtesy of VashiDonsk.