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Drug Effective in Rare Leukemia Mutations

CancerWise - January 2007

In a recent Phase I clinical study, the investigational agent MK-0457 was found to be the first effective treatment for rare but dangerous mutations in acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML) and myeloproliferative disorders (MPD).

Preliminary results of the study were published in the journal Blood in September 2006.

Significance of results

This study showed the first clinical activity of a kinase inhibitor against the:

  • T3151 BCR-ABL mutation found in CML and ALL
  • JAK-2 mutation in MPD

A kinase inhibitor is an agent designed to turn off an enzyme that causes abnormal growth in a cancer cell.

CML, ALL and MPD are relatively rare cancers, but they are aggressive and often fatal if standard therapy fails. Currently, no therapies specifically target these key mutations.

“This is a relatively small population that can potentially benefit from the experimental drug, but for those who have these mutations, this opens the door to a tremendous option for them,” said Francis Giles, M.D., professor in the Department of Leukemia at M. D. Anderson. “At present, there is no other targeted therapy we can offer them.”

Research methods

At M. D. Anderson and Duke University Medical Center, patients received the experimental drug intravenously over five days via ambulatory pumps. Patients were treated every two to three weeks.

Primary results

Thirty-five patients had leukemia and had undergone at least four prior unsuccessful types of therapy.

Of those with the T3151 mutation:

  • Eight of nine with CML responded
  • Both patients with ALL had:
    • Partial responses after two cycles
    • Complete responses after three cycles

Additional results

Patients experienced mild, but manageable, side effects, including:

  • Lowering of white blood cells
  • Hair loss
  • Nausea
  • Inflammation of the mouth


The primary objective of this Phase I study was to evaluate the safety of MK-0457 and to determine the maximum tolerated dose.

“While we went into this study to determine the safety and dosage of the experimental drug, it became apparent quite quickly that the drug was very well tolerated and showed clinical response,” Giles says. “As a result we ended the Phase I aspect of the study earlier than anticipated and moved into Phase II.”

According to the American Cancer Society, about 4,000 cases of ALL, 4,500 of CML and 10,000 of MPD are diagnosed each year. About 10% of patients have mutations for which no therapies are available.

The T3151 mutation is known to be responsible for the aggressive biological growth cycle and resistance to imatinib (Gleevec®), nilotinib (Tasigna®) and dasatinib (Sprycel®) in CML and ALL. These kinase inhibitors have been found to be effective in treating patients with leukemias that carry different mutations, but not against T3151.

What’s next?

Researchers have begun a multi-center, international Phase II trial of MK-0457 in CML. Look for information about this study in a future issue of CancerWise.

— From staff reports

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© 2015 The University of Texas MD Anderson Cancer Center