The FDA has approved Clolar for the treatment of children with a form of leukemia that has not responded to other treatments.
“Clolar is the first new leukemia treatment approved specifically for children in more than a decade,” says maker Genzyme in a news release. Genzyme expects to make Clolar available as quickly as possible in January.
Clolar is approved for children from 1 to 21 years old with acute lymphoblastic leukemia (ALL) that has not responded to two prior chemotherapy regimens. Genzyme says that studies have not yet shown improved survival with Clolar.
In 2005, an estimated 3,400 new cases of pediatric acute leukemia will be diagnosed in the U.S., says Genzyme. ALL is the most common form of childhood leukemia, and children who do not respond to initial treatment, or who relapse, have a very poor survival prognosis.
Clolar has received "orphan drug" designation for adult and childhood ALL. This classification is used for conditions that affect fewer than 200,000 people per year and in which a drug offers benefit over what’s currently available. Genzyme is required to continue to study Clolar to verify clinical benefit.
Clolar’s approval is based on a study of 49 children with ALL who had failed multiple previous chemotherapy regimens.
In the study, 30 percent of children improved with Clolar. Overall, 20 percent of all patients had a complete remission and 10 percent had a partial response.
One potentially serious side effect of Clolar is bone marrow suppression. This can decrease the number of immune system cells available to fight off severe infection. Other bone marrow cells, such as red blood cells, which carry oxygen, and platelets, which help blood clot, can also be affected. In this study, seven patients went on to receive bone marrow or stem cell transplants following treatment with Clolar.
Results of 12 additional patients were recently presented at the American Society of Hematology 46th Annual Meeting and Exposition in San Diego. These patients also had a 30 percent response rate.
"The children who participated in the CLOLAR study had failed an average of three prior treatment regimens and had very poor chances of survival," says lead researcher Sima Jeha, MD, in a news release. "As a pediatric oncologist, I am excited to have a new well-tolerated and effective treatment option for these patients with highly-resistant leukemia." Jeha is director of developmental therapeutics in the division of leukemia/lymphoma at St. Jude Children's Research Hospital.
Clolar is also being studied in children with another type of leukemia, acute myeloid leukemia (AML), who have failed other treatments. Among 42 children with AML, 26 percent have responded, with one complete remission and 10 partial remissions. Of these patients, 34 percent have gone on to receive a bone marrow transplant. The FDA has asked for more studies before approving Clolar for AML.
In addition to suppressing production of immune system cells in the bone marrow, Clolar can have other potentially serious side effects.
By killing leukemia cells in the bloodstream, Clolar can lead to the release of cell contents that could lead to a widespread inflammatory response in the body. Patients' breathing and blood pressure should be watched closely while Clolar is being given.
Clolar is given intravenously for one to two hours a day for five consecutive days. This is repeated for two to six cycles every 28 days depending on the response to treatment.
Heart problems, including a fast heart rate, fluid around the heart, and weakened heart pumping occurred in up to 35 percent of patients. However, Genzyme says it’s unclear if Clolar actually caused the problems.
Other side effects from Clolar include:
—Fever from low white blood cell count (cells that fight infection)
SOURCE: News release, Genzyme Corp.