Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Drug combination acts against aggressive chronic lymphocytic leukemia

11.12.2012
Ibrutinib, rituximab deliver a 1-2 punch to patients with few good options

A two-prong approach combining ibrutinib and rituximab (Rituxin®) to treat aggressive chronic lymphocytic leukemia (CLL) produced profound responses with minor side effects in a Phase 2 clinical trial at the University of Texas MD Anderson Cancer Center.

Researchers presented the results today at the 54th annual meeting of the American Society of Hematology (ASH).

"This is a patient population with a great need for more targeted therapies," said Jan Burger, M.D., Ph.D., associate professor in MD Anderson's Department of Leukemia. Burger was lead author of the study.

"Many CLL patients, especially those with indolent or non-aggressive disease, do well on the standard treatment of chemotherapy and antibodies," he said. "But for a certain subset of high-risk patients, treatment often fails, and remissions, if they are achieved, are short."

According to the National Cancer Institute's Surveillance Epidemiology and End Results database, CLL is the most common type of adult leukemia in the United States. An estimated 16,000 new cases will be diagnosed this year, and about 4,600 people will die because of the disease. Median age of diagnosis is 72, and it is more common in men than women.

Although chemotherapy combinations have improved the cure rate for CLL, side effects often are severe. A sizeable number of CLL deaths are from secondary cancers caused by treatment.

Early studies showed potential

Ibrutinib, a tyrosine kinase inhibitor that thwarts B-cell receptor signaling, is a promising new targeted therapy for mature B-cell malignancies, including certain types of myeloma and lymphoma. It has been shown to be especially effective in CLL.

Over the past two years, Phase 1/2 trials at MD Anderson and other sites showed high-risk CLL patients responded as well as low-risk patients to ibrutinib. However, the response often is lessened because of persistent lymphocytosis, an increase in leukemia cells in the blood due to release of CLL cells from the tissues (lymph glands) into the blood stream. Rituximab, a well-established antibody, was added to capture the CLL cells in the blood and thereby accelerate and improve response.

"When we looked at how well the high-risk patients were doing on ibrutinib - even though it was a small number - we saw a great opportunity to find out if combining the two drugs would have a positive impact on these patients," Burger said.

Combination tolerated well

Forty patients with high-risk CLL were enrolled in the study earlier this year. They received:
Daily oral doses of 420 mg ibrutinib throughout treatment
Weekly infusions of rituximab (375 mg/m2) weeks one through four
Monthly rituximab infusions for the next five months
At a median follow up of four months, 38 patients remained on ibrutinib therapy without disease progression. One patient died from an unrelated infectious complication, and one patient discontinued therapy due to oral ulcers.

Preliminary results: 85 percent response rate

Of 20 patients evaluated for early response at three months, 17 achieved partial remission for an overall response rate of 85%. Three achieved partial remission with persistent lymphocytosis.

Interestingly, lymphocytosis peaked earlier and the duration was shorter than with ibrutinib alone.

Treatment was well tolerated, with 13 cases of grade 3 or grade 4 toxicities, including neutropenia, fatigue, pneumonia, insomnia and bone aches. Most side effects were unrelated and transient. Many patients reported improved overall health and quality of life after three cycles of treatment.

"Although this study has a short follow-up time, we are encouraged by the fact that the vast majority of patients are responding and are able to continue on treatment, Burger said.

Development of ibrutinib for CLL crucial

Researchers said these data, together with the previous Phase 1/2 studies, emphasize the need for rapid further development of ibrutinib for high-risk CLL patients.

Pharmacyclics, the company that is developing ibrutinib, is proceeding with a Phase 3 multi-center clinical trial, in which MD Anderson will participate. Additionally, MD Anderson researchers will conduct a follow-up study on their research in high-risk CLL patients.

Other research team members from MD Anderson's Department of Leukemia included Michael Keating, M.D.; William Wierda, M.D., Ph.D.; Julia Hoellenriegel, M.S.; Alessandra Ferrajoli, M.D.; Stefan Faderl, M.D.; Susan Lerner, M.S.; Gracy Zacharian; Hagop Kantarjian, M.D.; and Susan O'Brien, M.D. Also participating were Xuelin Huang, Ph.D., of the Department of Biostatistics at MD Anderson; and Danelle James, M.D. and Joseph Buggy, Ph.D., of Pharmacyclics, Inc, Sunnyvale, CA.

Support for the study was provided by Pharmacyclics and CLL Global Research Foundation.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For nine of the past 11 years, including 2012, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Health and Medicine:

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Start codons in DNA may be more numerous than previously thought

21.02.2017 | Life Sciences

An alternative to opioids? Compound from marine snail is potent pain reliever

21.02.2017 | Life Sciences

Warming ponds could accelerate climate change

21.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>