Drug combination acts against aggressive chronic lymphocytic leukemia

December 10, 2012, University of Texas M. D. Anderson Cancer Center

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 , especially those with indolent or non-, 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 's Surveillance Epidemiology and End Results database, CLL is the most common type of 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, often are severe. A sizeable number of CLL deaths are from secondary cancers caused by treatment.

Early studies showed potential

Ibrutinib, a 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 in the blood due to release of CLL cells from the tissues () 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.

Explore further: Experimental agent may help older people with chronic leukemia

Related Stories

Experimental agent may help older people with chronic leukemia

May 16, 2012
The experimental drug ibrutinib (PCI-32765) shows great promise for the treatment of elderly patients with chronic lymphocytic leukemia (CLL), according to interim findings from a clinical trial.

Updated clinical results show experimental agent ibrutinib as highly active in CLL patients

December 9, 2012
Updated results from a Phase Ib/II clinical trial indicates that a novel therapeutic agent for chronic lymphocytic leukemia (CLL) is highly active and well tolerated in patients who have relapsed and are resistant to other ...

Novel experimental agent is highly active in CLL patients, interim study shows

December 11, 2011
An interim analysis of a phase Ib/II clinical trial indicates that a novel experimental agent for chronic lymphocytic leukemia (CLL) is highly active and well tolerated in patients who have relapsed and are resistant to other ...

B cell receptor inhibitor causes chronic lymphocytic leukemia remission

December 11, 2011
A new, targeted approach to treating chronic lymphocytic leukemia has produced durable remissions in a Phase I/II clinical trial for patients with relapsed or resistant disease, investigators report at the 53rd Annual Meeting ...

Decoding chronic lymphocytic leukemia

June 13, 2011
A paper published online on June 13 in the Journal of Experimental Medicine identifies new gene mutations in patients with chronic lymphocytic leukemia (CLL) -- a disease often associated with lack of response to chemotherapy ...

Recommended for you

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.