Genzyme Corporation and Berlex Oncology announced interim results from CAM307, an international confirmatory phase III clinical trial comparing alemtuzumab(Drug information on alemtuzumab) (Campath) with chlorambucil(Drug information on chlorambucil) (Leukeran) in previously untreated patients with progressive B-cell chronic lymphocytic leukemia (B-CLL). Preliminary results of the secondary endpoint from this study showed that patients who received the monoclonal antibody alemtuzumab exhibited significantly higher overall and complete response rates, with a manageable safety profile, compared with patients treated with chlorambucil. The data were presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO) in Atlanta.

Head-to-Head Comparison

The open-label, randomized trial with 297 patients compared the efficacy and safety of alemtuzumab to chlorambucil, which is considered by many to offer the most tolerable safety profile for previously untreated patients. The study examined a primary endpoint of progression-free survival and secondary endpoints that included safety, response rate, and overall survival.

As reported at ASCO, a prespecified independent interim review of the secondary endpoint data showed a nearly 30% greater (83% vs 56%) overall response rate among patients treated with alemtuzumab vs chlorambucil (P < .0001), and a 12-fold increase (24% vs 2%) in complete response rates in patients receiving alemtuzumab therapy (P < .0001).

In the comparison of safety parameters of alemtuzumab vs chlorambucil, the rates of grade 3/4 thrombocytopenia, anemia, and serious infections, other than cytomegalovirus, were found to be comparable between treatment arms. Although the rates of cytomegalovirus, neutropenia, and leukopenia were higher in the alemtuzumab arm, the difference in the incidence of febrile neutropenia was found to be insignificant.

A correlation between the cytogenetic profile of the patients participating in the CAM307 trial suggest statistically significant differences in overall and complete response rates observed in patients with certain cytogenetic abnormalities. Statistically significant higher response rates to alemtuzumab were observed in patients with a 13q deletion, a common genetic event observed in patients with B-CLL, and in the overall response rate of patients with 11q deletions, a cytogenetic abnormality typically associated with poor prognosis. In patients with a 17p deletion, another marker of poor prognosis, overall response rate was three times higher among patients receiving alemtuzumab vs those receiving chlorambucil—64% vs 20%, respectively. However, due to the small number of patients in this group (10 patients in the alemtuzumab arm and 11 patients in the chlorambucil arm), this trend did not reach statistical significance.

Novel Option for Poor-Risk Patients

Lead investigator Peter Hillmen, MB, CHB, of the Leeds General Infirmary, Leeds, UK, stated, "In addition to the excellent overall safety and efficacy findings we are observing thus far in CAM307, we also saw impressive responses in patients with poor prognostic cytogenetic abnormalities when treated with alemtuzumab. This group of poor-risk patients have very low response rates and a short survival when treated with conventional chemotherapy. The good results seen with alemtuzumab promise a novel, more effective therapeutic option for these patients with poor-risk CLL. We therefore look forward to receiving the final study results of alemtuzumab in relation to responses and survival in these difficult-to-treat populations."

Alemtuzumab received accelerated approval in 2001 and is currently indicated for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the drug's effectiveness is based on overall response rates.