Drug Combination Studied in Leukemias

Drug Combination Studied in Leukemias
Decitabine Paired With Valproic Acid

Cancer researchers are conducting a clinical trial to study a combination of drugs they hope will provide a less toxic and more effective treatment alternative for patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).

Significance of the study

The M. D. Anderson study involves the drug decitabine (Dacogen), which has been shown to be effective in the treatment of MDS, and valproic acid (Depakene), which researchers hope may increase the treatment's effectiveness.

"AML and MDS are often resistant to treatment, and prognosis for many patients is poor," says Jean-Pierre Issa, M.D., professor in the Department of Leukemia at M. D. Anderson and principal investigator on the study.

Other than bone marrow transplants or highly toxic chemotherapy for the small minority of patients who qualify, supportive care or clinical trials are often the only treatment options. Many times the risks of treatment outweigh the possible benefits for older patients.

Study description

This randomized Phase II trial is separated into two arms, or sections. One group of patients will receive only decitabine; the other will receive a combination of decitabine and valproic acid.

During each one-month treatment cycle, patients receive infusions of the drug(s) for five consecutive days the first week, then once or twice per week for the next three weeks.

The initial recruitment goal is 40 patients, 20 in each arm. After this number has been reached and the initial study progresses, researchers will continue to enroll additional participants, adjusting recruitment to enroll more patients in the better-performing arm. When one arm is clearly more effective, the study will end.

Criteria

To be considered for this study, patients must:

• Have had no previous high-dose chemotherapy
• Have a life expectancy of greater than eight weeks
• Have normal organ function
• Not have a central nervous system disorder

Possible side effects

In prior studies, the incidence of side effects for both study drugs has been low, with reduced white blood cell counts, platelet counts and red blood cell counts being the most prevalent. Common side effects of chemotherapy, such as nausea or hair loss, have not occurred.

Background

Decitabine is one of a new class of drugs, called DNA methyltranferase inhibitors, which restore normal function to silenced genes that ordinarily suppress the development of AML and MDS. The drug also is being studied in treatment of many other types of cancer.

Previously, Issa led a team of researchers that found decitabine is more effective when given to AML and MDS patients at very low doses for a longer period of time.

The studies showed decitabine yielded a:

• Complete response in 40% of patients
• Partial response in as many as 70% of patients

Decitabine, which received fast-track approval from the U.S. Food and Drug Administration (FDA) earlier this year, is the standard of care for MDS at M. D. Anderson. Now researchers are looking at drugs to combine with it to further improve outcomes.

"Valproic has been in use for decades as an anti-seizure drug," Issa says. "It has a reputation as being safe, and it synergizes nicely with decitabine."

For more information about the study or to enroll participants, call askMDAnderson at 1-877-MDA-6789 (1-877-632-6789) and ask for information about protocol 2006-0686.