Navigation Links
Drug combination acts against aggressive chronic lymphocytic leukemia
Date:12/10/2012

ATLANTA - 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.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-516-4855
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Scientists test 5,000 combinations of 100 existing cancer drugs to find more effective treatments
2. Combination treatment may improve survival of breast cancer patients with brain metastases
3. Drug combination against NRAS-mutant melanoma discovered
4. Combination peptide therapies might offer more effective, less toxic cancer treatment
5. DNDi and Cipla to develop 4-in-1 pediatric antiretroviral drug combination
6. BUSM in vitro study identifies potential combination therapy for breast cancer
7. Moffitt Cancer Center researchers test drug combinations to prevent graft vs. host disease
8. Discovery suggests new combination therapy strategy for basal-like breast cancers
9. Cancer vaccine combination therapy shows survival benefit in breast cancer
10. Combination of 2 drugs reverses liver tumors
11. Immunotherapy for elderly cancer patients finds new promise in drug combination
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Drug combination acts against aggressive chronic lymphocytic leukemia
(Date:2/11/2016)... ... February 11, 2016 , ... Be Well Medical ... in the heart of Old Town at 108 South Columbus St, Suite 201, Alexandria, ... highest level of medical care in the convenience of their homes, offices or at ...
(Date:2/11/2016)... Southborough, MA (PRWEB) , ... February 11, 2016 , ... ... avoid overpaying for IT services, what questions to ask your IT consultant before signing ... them access to your computer network. , “With companies relying heavily on e-mail and ...
(Date:2/10/2016)... (PRWEB) , ... February 10, 2016 , ... ... practitioner, is known locally for a series of therapeutic sessions to help Los ... their characters and in their lives. The series, known as “Mindfulness for Actors ...
(Date:2/10/2016)... ... February 10, 2016 , ... MetLoop CEO Jay Southerland announced ... at the International Roofing Expo in Orlando, Florida on February 17-19. , With ... weather technology in the hands of consumers, roofing contractors, manufacturers and distributors,” Southerland ...
(Date:2/10/2016)... TX (PRWEB) , ... February 10, 2016 , ... ... commencement of a master charity program created to assist the local community. Pledging ... with community leaders and nonprofit organizations in the area. Their goal is to ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016  Galmed Pharmaceuticals Ltd. (Nasdaq: ... on the development of a once-daily, oral therapy for ... Chief Medical Officer, Dr. Maya Halpern , has notified ... Chief Medical Officer and from its Board of Directors ... reaching retirement age. Allen Baharaff . Mr. ...
(Date:2/11/2016)... February 11, 2016 North America ... published by MarketsandMarkets, The global market is expected to reach USD ... at a CAGR of 10.2%. --> North America ... 2020", published by MarketsandMarkets, The global market is expected to reach ... growing at a CAGR of 10.2%. --> According to ...
(Date:2/10/2016)... February 11, 2016 ... the "Molecular Diagnostics Reports Bundle" ... http://www.researchandmarkets.com/research/rp4pg8/molecular ) has announced the addition of ... report to their offering. --> ... announced the addition of the "Molecular ...
Breaking Medicine Technology: