Featured Research

from universities, journals, and other organizations

Drug Shown To Be Clinically Active Against Multiple Target Mutations In Two Types Of Leukemia And Myeloproliferative Disorders

Date:
December 21, 2006
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Researchers at the University of Texas M. D. Anderson Cancer Center report that MK-0457 (VX-680), a novel multi-kinase inhibitor, is clinically active against multiple target mutations in two types of leukemia and myeloproliferative disorders, and produces few side effects for patients.

Researchers at The University of Texas M. D. Anderson Cancer Center report that MK-0457 (VX-680), a novel multi-kinase inhibitor, is clinically active against multiple target mutations in two types of leukemia and myeloproliferative disorders, and produces few side effects for patients.

Francis J. Giles, M.D., professor in the Department of Leukemia at M. D. Anderson Cancer Center, presented the Phase I / II trial data at the annual meeting of the American Society of Hematology.

According to Giles, the study of 44 patients, conducted at M. D. Anderson Cancer Center and Duke University Medical Center, showed the first clinical activity of a kinase inhibitor against the T315I BCR-ABL mutation found in chronic myeloid leukemia (CML) and acute lymphocytic leukemia (ALL). In addition, the trial showed the first activity against the JAK-2 mutation found in myeloproliferative disorders (MPD), a group of blood diseases that can evolve into leukemia. MK-0457 has also been found in previous studies to inhibit Aurora kinases A, B, C and FLT3 in leukemias.

Giles reported that patients on the study experienced minimal side effects, such that no maximum tolerated dose was defined. Mild side effects included lowering of white blood cells, hair loss, nausea and inflammation of the mouth.

"MK-0457 is a drug that produces clinical and biologic activity where we have not seen it before - in T315I-positive CML and ALL and JAK-2-positive MPD. This is a very active biologic agent for patients with advanced leukemia, and has very few side effects, all of which are quite manageable," Giles said. "With the data from this trial, we have a strong rationale to take this agent forward to more definitive and larger studies."

Though CML, ALL and MPD are relatively rare cancers, they are very aggressive and often fatal after failing standard therapy, said Giles. For the subset of leukemia patients who have the T315I mutation or for MPD patients with the JAK-2 mutation - about 10 percent of patients with the respective diagnoses - there are no therapies available to specifically attack these key mutations.

"This is a relatively small population that can potentially benefit from the drug, but for those who have these mutations, this research opens the door to a tremendous option for them," said Giles. "At present, there is nothing to offer them."

According to the American Cancer Society, there are about 4,000 new cases of ALL, about 4,500 new cases of CML and about 10,000 new cases of MPD diagnosed each year.

The T315I 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 treating patients with leukemias who carry different mutations.

According to the study, the 35 leukemia patients on the study had at least four prior types of therapy, many of who received at least one of the three standard chemotherapies. The nine MPD patients' treatments ranged from one to seven prior lines of therapy.

But because of the mutations associated with resistance to these treatments, the patients did not respond until they were given the intravenous MK-0457 for five consecutive days. Of the patients with the T315I mutation, eight of nine patients with CML responded as did both of the T315I-positive ALL patients who had a partial response after the second cycle and complete response after the third cycle of treatment respectively.

"While we went into this trial to determine the safety and dosage of the drug, it became apparent quite quickly that the drug was very well tolerated and showing clinical response not only in patients but in terms of pharmacodynamics," said Giles. "As a result, we ended the Phase I aspect of the trial earlier than anticipated and moved into Phase II with a range of different doses to safely prescribe, depending on the patient's condition and outlook. We are quite hopeful that this drug will be beneficial for this segment of patients, but additional research will be needed."

Giles and his team are planning to begin later this month an international Phase II study of MK-0457 in patients with the T315I mutation.

Merck and Co. is currently conducting clinical trials of MK-0457 in various cancer types as part of a collaboration with Vertex Pharmaceuticals Incorporated. Merck and Co. holds worldwide and commercialization rights to MK-0457. MK-0457 (VX-680) was discovered by Vertex Pharmaceuticals.


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. "Drug Shown To Be Clinically Active Against Multiple Target Mutations In Two Types Of Leukemia And Myeloproliferative Disorders." ScienceDaily. ScienceDaily, 21 December 2006. <www.sciencedaily.com/releases/2006/12/061211124008.htm>.
University of Texas M. D. Anderson Cancer Center. (2006, December 21). Drug Shown To Be Clinically Active Against Multiple Target Mutations In Two Types Of Leukemia And Myeloproliferative Disorders. ScienceDaily. Retrieved October 23, 2014 from www.sciencedaily.com/releases/2006/12/061211124008.htm
University of Texas M. D. Anderson Cancer Center. "Drug Shown To Be Clinically Active Against Multiple Target Mutations In Two Types Of Leukemia And Myeloproliferative Disorders." ScienceDaily. www.sciencedaily.com/releases/2006/12/061211124008.htm (accessed October 23, 2014).

Share This



More Health & Medicine News

Thursday, October 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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