Celator Pharmaceuticals, Inc., a pharmaceutical company developing new and more effective therapies to treat cancer, have enrolled patients in an investigator-initiated clinical study evaluating CPX-351 (cytarabine:daunorubicin) Liposome Injection in patients with untreated high-risk myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML), excluding acute promyelocytic leukaemia, at high risk of treatment-related mortality.

A recent analysis of 3,365 adults with newly diagnosed AML treated on protocols at Southwest Oncology Group (SWOG) or at MD Anderson Cancer Centre (MDA) indicated that the weekly risk of death falls sharply once four weeks elapse from the start of intensive induction chemotherapy. This observation suggests that patients at high-risk for early mortality comprise a qualitatively distinct group and may be defined and objectively identified using an algorithm with a scoring system (TRM score) based on performance status, age, platelet count, albumin, secondary AML, white blood cell count, peripheral blood blast percentage and creatinine. Analysis of the combined SWOG and MDA experience suggests that approximately 20 per cent of newly diagnosed adults with AML meet this entry criterion.

To be eligible for the study, patients must have a high TRM score, indicating increased risk for treatment-related mortality. The study, which could enroll up to 90 patients, will evaluate two different doses of CPX-351 in patients deemed at high risk of TRM to determine whether CPX-351 could be an option in these patients. The rationale for evaluating CPX-351 in this protocol is based on two observations from phase I and II studies of CPX-351. First, complete response was observed in patients with relapsed or refractory AML at dose levels well below the maximum tolerated dose (MTD), allowing lower doses to be tested in more fragile patients. Second, CPX-351 reduced early mortality among intensively treated newly diagnosed older patients, while retaining the same overall response rates, resulting in a net improvement in survival among high-risk AML patients (most notably in patients with secondary disease).

"The need for efficacious treatments in medically unfit patients with AML or high-risk MDS is unquestioned," said Roland Walter, MD, PhD, assistant member of the Clinical Research Division at the Fred Hutchinson Cancer Research Centre, who enrolled the first patient. "Many of these individuals - or elderly patients more generally - are often excluded from curative-intent or even lower-intensity therapy, although the potential benefit of disease-directed therapy is well established. This trial provides an exciting opportunity to test a novel therapy in a patient population that is often neglected in the typical AML trial."

"As Celator continues to enroll patients in a phase III study in patients with secondary AML, it's important to evaluate the potential benefit CPX-351 may provide in other patient populations," said Scott Jackson, chief executive officer of Celator Pharmaceuticals. "Working with investigators at the Fred Hutchinson Cancer Research Centre, and potentially other leading centres, will help the company evaluate if CPX-351 offers a benefit in this patient population, a patient population in need of therapeutic improvements."