Biopharmaceutical company Cell Therapeutics, Inc. (CTI) and Chroma Therapeutics Ltd, a drug development company focused in the fields of oncology and inflammatory disorders, announced that the results from the OPAL phase II study of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (AML) have published in  Lancet Oncology. Tosedostat is an oral aminopeptidase inhibitor which has been shown to deprive tumor cells of the amino acid building blocks they need to make proteins necessary for tumor cell survival.

The lead author was Dr. Jorge Cortes, Professor of Medicine and Internist, Department of Leukaemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Centre in Houston, Texas.

The trial showed that once-daily oral tosedostat resulted in a disease control rate of 51 per cent. Subset analyses suggested the greatest benefit occurred in the difficult-to-treat patients with prior myelodysplastic syndrome (MDS) or those that had received prior hypomethylating therapy (HMA). Adverse events were mild, predictable and manageable.

This phase II multi-centre, randomized study evaluated the safety and efficacy of two dose regimens of tosedostat to determine an appropriate regimen for future clinical studies. The study enrolled 73 patients randomized to two treatment arms: tosedostat 120 mg once daily for six months or 240 mg once daily for two months followed by 120 mg once daily for four months. The median age of the patients was 72 years old. Prior primary induction therapy for AML included 58 per cent of the patients treated with Ara-C plus anthracycline or other Ara-C regimens, 36 per cent of the patients treated with HMAs and seven per cent of the patients treated with other regimens. Fifty-two per cent had been refractory to primary induction therapy.

"There are limited therapeutic options available for elderly patients who, after failing hypomethylating therapy, experience AML progression from MDS," said Dr Cortes. "The novel mechanism of action and observed response rate in this completed phase II study suggests that tosedostat could address this unmet medical need. We are currently conducting a phase II study investigating the combination of tosedostat with azacytidine - an HMA, or low-dose cytarabine, a standard leukaemia therapy in patients with relapsed or refractory AML and MDS - to determine if tosedostat would be safe and more effective when used in combination with these agents."

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 myelodysplastic syndrome (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. The symptoms of AML are caused by replacement of normal bone marrow with leukaemic 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.

Tosedostat is an oral, aminopeptidase inhibitor that has demonstrated significant anti-tumour responses in blood-related cancers and solid tumours in phase I-II clinical trials. CTI has exclusive marketing and co-development rights to Chroma Therapeutics Ltd.'s drug candidate tosedostat in North, Central and South America.

Cell Therapeutics, Inc. is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable.