ATLANTA—Alemtuzumab (Campath) is well tolerated when given as front-line therapy for progressive B-cell chronic lymphocytic leukemia (BCLL) and produces a higher response rate than chlorambucil(Drug information on chlorambucil) (Leukeran). These were the key interim findings of a phase III trial presented at the 2006 ASCO Annual Meeting (abstract 6511).

Based on phase II trial data, FDA granted accelerated approval for alemtuzumab(Drug information on alemtuzumab) for the treatment of BCLL in patients who have been treated with alkylating agents and who have had a failure on fludarabine (Fludara) therapy, said Peter Hillmen, MB, ChB, PhD, of Leeds General Infirmary, UK. "Following the approval, there was a postapproval commitment to perform a randomized controlled trial against one of the approved agents," he explained, and chlorambucil was chosen.

A total of 297 patients with untreated progressive BCLL were enrolled in the trial (CAM307) in Europe and the United States, and randomized to alemtuzumab (30 mg IV three times a week for up to 12 weeks) or chlorambucil (40 mg/m² PO every 28 days for up to 12 months). Patients in the alemtuzumab arm were given prophylactic therapy to avert Pneumocystis carinii pneumonia and herpesvirus infection.

Response Rates

Responses were assessed by bone marrow biopsy according to NCI criteria, Dr. Hillmen said. When responses were assessed by investigators, the overall rate of response (complete plus partial responses) was significantly higher with alemtuzumab than with chlorambucil (77% vs 39%); there was also a significant difference in favor of alemtuzumab in terms of complete responses (31% vs 4%). Similarly, when responses were assessed by an independent response review panel, alemtuzumab was significantly superior to chlorambucil in terms of overall response rate (83% vs 56%) and complete response rate (24% vs 2%).

He noted that the study showed significantly higher overall response rates in patients with certain cytogenetic abnormalities, including those with 13q deletions, a common genetic event in BCLL, and 11q deletions, an abnormality typically associated with poor prognosis.

Further, he said, in patients with a 17p deletion, another marker of poor prognosis, overall response rates were three times higher among patients receiving irinotecan(Drug information on irinotecan) (64% vs 20%), but the number of patients was too small to reach significance.

"We hope that later on this year we will have progression-free survival data when sufficient patients have progressed within the trial," Dr. Hillmen said.

Toxicity