Featured Research

from universities, journals, and other organizations

Phase I trial indicates ponatinib may thwart most resistant chronic myeloid leukemia

Date:
December 6, 2010
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
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 report.

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.

Related Articles


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 leukemia cells in the bone marrow) among two groups of patients:

  • Those who have tried two or three of the drugs that have revolutionized treatment of CML -- imatinib (Gleevec), nilotinib (Tasigna) and dasatinib (Sprycel) -- and developed resistance to them.
  • And those whose leukemia cells carry the T315I mutation, which resists all current therapies.

"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 mutations 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:

  • 30 of 32 patients (94 percent) in CML chronic phase had complete hematologic responses; 20 (63 percent) had major cytological responses, 12 complete and eight partial. Of these 20 cytogenetic responders, 18 remained on the treatment with no disease progression.
  • All 11 chronic phase CML patients who had the T315I mutation had complete hematologic response and nine had major cytogenetic responses, eight of which were complete.
  • For 16 CML patients in accelerated or blast phase or with Philadelphia-positive acute lymphocytic leukemia, five (31 percent) had a major hematological response and three (19 percent) had a major cytogenetic response.
  • Of nine CML patients in accelerated or blast phase or with Ph+ALL who also carried the T315I mutation, three (33 percent) had major hematologic response and two (22 percent) had major cytogenetic response.

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.

The trial was funded by ARIAD.

Co-investigators with Cortes are Hagop Kantarjian, M.D., MD Anderson Department of Leukemia; Moshe Talpaz, M.D., and Dale Bixsby of the Comprehensive Cancer Center at the University of Michigan; Michael Deininger, M.D., Ph.D., and Michael Mauro, M.D., Center for Hematologic Malignancies, Oregon Health & Science University, Portland, OR; Neil Shah, M.D., University of California, San Francisco; Ian Flinn, M.D., Ph.D., Sarah Cannon Research Institute, Nashville, TN.; Thomas O'Hare, Ph.D., Oregon Health and Science University, Howard Hughes Medical Institute, Portland, OR.; and Simin Hu, Ph.D., Rebecca Kan, Victor Rivera, Ph.D., Tim Clackson, Ph.D. and Frank Haluska, M.D., Ph.D., of ARIAD Pharmaceuticals, Cambridge, MA.


Story Source:

The above story is based on materials provided by University of Texas M. D. Anderson Cancer Center. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas M. D. Anderson Cancer Center. "Phase I trial indicates ponatinib may thwart most resistant chronic myeloid leukemia." ScienceDaily. ScienceDaily, 6 December 2010. <www.sciencedaily.com/releases/2010/12/101206093713.htm>.
University of Texas M. D. Anderson Cancer Center. (2010, December 6). Phase I trial indicates ponatinib may thwart most resistant chronic myeloid leukemia. ScienceDaily. Retrieved March 6, 2015 from www.sciencedaily.com/releases/2010/12/101206093713.htm
University of Texas M. D. Anderson Cancer Center. "Phase I trial indicates ponatinib may thwart most resistant chronic myeloid leukemia." ScienceDaily. www.sciencedaily.com/releases/2010/12/101206093713.htm (accessed March 6, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, March 6, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Bupa Eyes India Healthcare Opportunities

Bupa Eyes India Healthcare Opportunities

Reuters - Business Video Online (Mar. 5, 2015) Bupa is hoping to expand in India&apos;s fast-growing health insurance market, once a rule change on foreign investment is implemented. The British private healthcare group&apos;s CEO tells Grace Pascoe why it&apos;s so keen on the new opportunity. Video provided by Reuters
Powered by NewsLook.com
Doctor in Your Pocket Is Getting Smarter

Doctor in Your Pocket Is Getting Smarter

Reuters - Business Video Online (Mar. 5, 2015) Mobile apps are turning smartphones into a personal doctors, with users able to measure heart rate, blood pressure and even blood sugar. But will it change our behaviour? Ivor Bennett reports from the Mobile World Congress in Barcelona. Video provided by Reuters
Powered by NewsLook.com
AbbVie Inks $21B Deal To Buy Cancer Drugmaker Pharmacyclics

AbbVie Inks $21B Deal To Buy Cancer Drugmaker Pharmacyclics

Newsy (Mar. 5, 2015) AbbVie announced Wednesday it will buy cancer drugmaker Pharmacyclics in a $21 billion deal. Video provided by Newsy
Powered by NewsLook.com
Toddlers Drinking Coffee? Why You Shouldn't Share Your Joe

Toddlers Drinking Coffee? Why You Shouldn't Share Your Joe

Newsy (Mar. 5, 2015) A survey of Boston mothers and toddlers found that 15 percent of two-year-olds drink coffee and 2.5 percent of 1-year-olds. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins