Navigation Links
Phase I trial indicates ponatinib may thwart most resistant CML

ORLANDO 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 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.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Assessing positive outcomes of phase III trials
2. Professor Zvi Ram presents phase III recurrent glioblastoma survival and quality of life data from the first pivotal study of the NovoTTF-100A at 15th Annual Society for Neuro-Oncology Scientific Meeting
3. Nutrition rating enhancing front-of-package nutrition rating systems and symbols: Phase 1
4. New Phase II study shows first-line promise of lung cancer drug PF-299
5. Pazopanib shows promise in Phase II trial for relapsed/refractory urothelial cancer
6. Phase III study shows everolimus delays tumor progression in hard-to-treat neuroendocrine tumors
7. Front-of-package symbols and systems: IOM phase 1 report
8. Vaccine extends glioblastoma patients survival in phase II trial
9. Operation Unified Response: 3 phases of disaster care in Haiti
10. Aeras and Crucell announce Phase II clinical trial start in Kenya
11. Sickle cell treatment developed at LA BioMed enters Phase 3 clinical trial
Post Your Comments:
Related Image:
Phase I trial indicates ponatinib may thwart most resistant CML
(Date:11/25/2015)... ... November 25, 2015 , ... “While riding the bus, I ... Bronx, N.Y. “I thought there had to be a convenient and comfortable way to ... The PROTECTOR enables disabled individuals to safely travel during cold or inclement weather. In ...
(Date:11/25/2015)... , ... November 25, 2015 , ... ... (PHA) announces the nation’s Periwinkle Pioneers, individuals and groups responsible for advancing care ... disease. The Periwinkle Pioneers, nominated by the public, will receive special recognition throughout ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... philanthropic seniors, is resulting in a way for homeless people to have a ... have launched a new initiative whereby they are repurposing plastic bags into sleeping ...
(Date:11/25/2015)... ... November 25, 2015 , ... Since its launch in 2012, ... adult stem cell therapies to patients with chronic degenerative medical conditions. Now, the ... Registered Trademark (RTM). , Organizations are required to hold a registered trademark in ...
(Date:11/24/2015)... ... November 25, 2015 , ... Genesis Chiropractic Software ... software creates an agreement between the practice owner and the patient that automatically ... notification, and projections. Click here to learn more. , ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... FRANCISCO , Nov. 24, 2015  Thanks to ... Dignity Health St. Mary,s Medical Center,s Sister Diane Grassilli ... breast imaging capabilities in San Francisco ... an anonymous friend, stepped forward with a gift of ... for Breast Digital Mammography with Tomosynthesis and Whole Breast ...
(Date:11/24/2015)... Colo. , Nov. 24, 2015  Array ... that its Chief Executive Officer, Ron Squarer ... Healthcare Conference in New York.  The public is ... webcast on the Array BioPharma website.Event:Piper Jaffray Annual ... , Wednesday, December 2, 2015Time:1:30 p.m. Eastern Time ...
(Date:11/24/2015)... HOUSTON, TX and VANCOUVER, Nov. 24, 2015 /PRNewswire/ ... EPI; NASDAQ: EPIX ) announced today that the ... clinical study of EPI-506 as a treatment for metastatic ... States and Canada.  --> ... --> In the Phase 1/2 clinical trial, ...
Breaking Medicine Technology: