Phase I trial indicates ponatinib may thwart most resistant CML

December 6th, 2010 in Medicine & Health / Cancer

A new drug appears to help chronic myeloid leukemia patients who are out of treatment options after first- and second-line drugs have failed them or because their cancer cells have a mutation that makes them resistant from the start, researchers reported at the 52nd Annual Meeting of the American Society of Hematology.

In a Phase I clinical trial, the drug ponatinib produced major or complete hematologic responses (absence of CML cells in the blood) and cytogenetic responses (absence of in the ) among two groups of patients:

"Ponatinib seems to be filling the gap we had for patients who right now have no good treatments left," said Jorge Cortes, M.D., professor in The University of Texas MD Anderson Cancer Center Department of Leukemia, who presented the group's findings. "We are very encouraged by such strong results in the Phase I setting and have begun a pivotal Phase II clinical trial."

Preclinical research had indicated that ponatinib, developed by ARIAD Pharmaceuticals, inhibits all that cause resistance to drugs that stifle the BCR-ABL protein which drives CML. BCR-ABL is produced by the aberrant gene bcr-abl, which occurs when two chromosomes swap portions of their DNA from separate bcr and abl genes. The abnormality is called the Philadelphia chromosome.

As of July 2010, 67 patients were enrolled in the study: 57 with CML, including 42 in the chronic, or early, stage, seven in the accelerated stage and eight in the blast phase, the most advanced form of the disease. Three had Philadelphia-positive acute lymphoblastic leukemia, three had acute myeloid leukemia and four were divided among other blood malignancies.

A total of 48 patients were evaluable at the time of reporting. Of these:

Researchers also noted responses in patients with heavily resistant disease with no mutations and among patients with other mutations resistant to existing drugs.

The most common side effects were low platelet counts (24 percent of patients), headache (14 percent), nausea (14 percent), joint pain (13 percent), fatigue (13 percent), anemia (11 percent), increased lipase (11 percent), muscle spasms (11 percent), rash (11 percent), muscle pain (10 percent) and pancreatitis (10 percent). All dose-limiting toxicities were reversible.

Provided by University of Texas M. D. Anderson Cancer Center

"Phase I trial indicates ponatinib may thwart most resistant CML." December 6th, 2010. http://phys.org/news/2010-12-phase-trial-ponatinib-thwart-resistant.html