ChemGenex launches multinational phase 2/3 study for CML patients with T315I mutation

07-12-2006

ChemGenex Pharmaceuticals (CXS; CXSP) announced that it has launched a new multinational phase 2/3 study evaluating the use of Ceflatonin (homoharringtonine, HHT) in patients with chronic, accelerated and blast-phase chronic myeloid leukemia (CML) who have the T315I bcr-abl point mutation, which is associated with resistance to Gleevec and two known tyrosine kinase inhibitors (TKIs) currently under development.

The study will be conducted in both the United States and Europe and is projected to enroll up to 81 patients within 12 months. The primary endpoint will be hematologic response rate, and the secondary endpoint will be cytogenetic response rate.

"This new study offers hope to a growing number of CML patients who have developed the T315I bcr-abl point mutation, against which both Gleevec, and two investigational TKI's, are ineffective," said Greg Collier, PhD, chief executive officer and managing director of ChemGenex. "Ceflatonin has recently shown preclinical activity in CML cell lines with the T315I mutation and has already demonstrated clinical activity in human clinical studies for patients failing Gleevec. Demonstration of positive results in CML patients with the T315I mutation may serve as the basis for filing for an NDA with the FDA under an accelerated approval, based on a high level of unmet medical need."

In other developments, a recent preclinical study presented at the American Association of Cancer Research conference showed that Ceflatonin is active as a single agent and in combination with other agents, including imatinib (Gleevec), in CML cell lines with the T315I bcr-abl point mutation. The research was conducted by Professor William Plunkett, PhD, Department of Experimental Therapeutics at the University of Texas M.D. Anderson Cancer Center.

The trial will be a multinational, open-label study which will open initially at the M.D. Anderson Cancer Center in Houston, Texas, the University of Heidelberg in Germany, and the Hospital Edouard Herriott in Lyon, France. The trial will expand to approximately 16 additional centers in both the United States and Europe.

In the remission induction phase, patients will receive 1.25 mg/m2 HHT by subcutaneous injection two times a day for 14 consecutive days, with cycles repeated every 28 days. In the remission maintenance phase, patients will receive 1.25 mg/m2 HHT by subcutaneous injection two times a day for 7 consecutive days, with cycles repeated every 28 days. Patients will be stratified upon whether they have chronic phase (CP), accelerated phase (AP), or blast phase (BP) CML. The study will be conducted in two stages, using a Simon two-stage study design for each patient subpopulation.

During the first stage, 13 evaluable patients from each patient subpopulation (CP, AP, BP CML) will be enrolled. If one or more responses are seen during the first stage of a subpopulation, another 14 evaluable patients from that subpopulation will be enrolled in the second stage. It is anticipated that a maximum of 81 patients will be enrolled into the study, if all three subpopulations proceed to the second stage. The primary and secondary endpoints are hematologic and cytogenetic response rates, respectively.

Ceflatonin (HHT) is a potent inducer of apoptosis (programmed cell death) in myeloid cells and inhibits angiogenesis (blood vessel formation). In Phase 2 studies, Ceflatonin has demonstrated clinical activity in patients with CML, both as a single agent and in combination with other chemotherapeutic drugs. ChemGenex is developing Ceflatonin for the treatment of CML, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

Because Ceflatonin has a different mechanism of action than tyrosine kinase inhibitors, clinical studies are being planned to determine if 1) Ceflatonin will be useful in treatment of CML patients who have developed resistance to TKI therapy due to development of the T315I BCR-ABL point mutation; 2) to assess activity of Ceflatonin in CML patients who have failed TKI's; and 3) to assess if combination therapy with Ceflatonin, TKI's and other agents will increase the cytogenetic and molecular response rates in CML patients.

Ceflatonin is not approved by the FDA as a treatment in any indication and is currently being evaluated in clinical trials for efficacy and safety for future regulatory applications.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2006, Biotech Business Week via NewsRx.com.