Drug Could Augment or Replace Gleevec

Positive Results Seen for Chronic Myeloid Leukemia (CML)

An oral investigational drug, AMN107, is producing powerful responses for people resistant to Gleevec, the medication that helps most chronic myeloid leukemia (CML) patients. The strength of the drug may be so powerful that it could one day replace Gleevec, researchers say.

AMN107 is showing tremendous results in an ongoing clinical trial, says the study's principal investigator Hagop Kantarjian, M.D., professor and chair of M. D. Anderson's Department of Leukemia.

"AMN107 is a much more powerful drug than Gleevec, and, I believe, may become the new standard of treatment in CML, either alone or in combination with Gleevec," Kantarjian says.

Study shows results quickly

More positive data would be needed in order for AMN107 to replace Gleevec, he says, but preliminary results in the AMN107 study alone are impressive.

Results of the study, being conducted with the University of Frankfurt in Germany, were presented in April at the annual meeting of the American Association for Cancer Research (AACR).

Study results included normal blood counts for more than:

• 90% of patients in the "chronic" CML phase
• 70% of patients in the "accelerated" (advanced) phase
• 50% of patients in the "blast" (terminal) phase

What causes the disease?

CML is caused by the swapping of genetic material in bone marrow stem cells that produces an abnormality called the Philadelphia chromosome. This chromosome contains a new, fused gene, BCR-ABL, which produces an enzyme that prompts uncontrolled cell growth. Gleevec binds to this BCR-ABL enzyme, often killing the leukemia cell.

For a few patients like Becky Roller, however, Gleevec fails. Roller began taking Gleevec in May 2000. While her response was not perfect, her blood counts stabilized. But in 2004, Gleevec stopped working.

Roller then became one of the first three patients to enter the AMN107 trial. At the time, she didn't realize she was in the terminal stages of CML. Her response to AMN107 was strong. Side effects for her and most patients have been minimal, and the drug has allowed her to live a normal life.

Study moves to Phase II

AMN107 is 30 to 100 times more potent than Gleevec because it more efficiently binds to BCR-ABL, and is active against most mutated forms of BCR-ABL that can produce Gleevec resistance, says Francis Giles, M.D., co-principal investigator on the study who presented the results at AACR. Giles is a professor of medicine in M. D. Anderson's Department of Leukemia.

"At this time, CML patients who are responding well to Gleevec do not need to switch to AMN107," Giles stresses. "Gleevec is a very effective agent and failures are very rare in patients with early stage disease."

Because of the established activity and safety of AMN107, a Phase II study will open soon for newly diagnosed CML patients, Kantarjian says. Another six studies are testing the drug in all three CML phases, as well as in other types of leukemia.

For more information, please contact the M. D. Anderson Information Line at 1-800-392-1611, option 3.