Genzyme says that its combination treatment of Campath® and Fludara® (FluCAM) for chronic lymphocytic leukemia (CLL) fared better than Fludara alone in Phase III trials. Based on the study’s positive preliminary findings, Genzyme intends to seek regulatory approvals to further broaden the Campath label to include its use along with Fludara.
This data comes from a planned second interim analysis, and final efficacy and safety data from the study are expected to be available in the second half of 2010. The trial’s data-safety monitoring panel recommended early closure of the study as it had achieved the prespecified clinical and statistical significance in progression free survival (PFS), the study’s primary endpoint.
Response data thus far indicates that the FluCAM combination provided significantly higher overall and complete response rates compared to Fludara alone, both secondary endpoints. Another secondary target of overall survival, however, did not reach significance.
The median PFS was 29.6 months for patients on the FluCAM regimen compared to 20.7 months for those on Fludara, reducing the risk of disease progression or death by 39%. In the subgroup of patients with advanced, Rai stage III-IV CLL, the median PFS was 26.1 months for FluCAM and 12.1 months for Fludara. In addition, the overall response rate of patients on FluCAM was 84.8% compared to 67.9% on Fludara. The complete response rate was 30.4% on FluCAM versus 16.4% on Fludara.
“There are limited published randomized trial data evaluating treatment regimens specifically in the second-line setting for patients with chronic lymphocytic leukemia, contributing to the wide variability in treatment patterns seen in this setting,” points out Cyndi Sirard, M.D., medical director, Genzyme transplant and oncology. “The trial advances our understanding of how to use Campath in combination with Fludara and may offer an alternative to existing regimens used in this setting.”
The Phase III study was a multicenter, international, open-label, randomized trial that included 335 patients with progressive Rai stage I-IV CLL. It investigated whether treatment of patients with relapsed or refractory CLL with FluCAM was more beneficial than treatment with Fludara alone. Patients in the trial received one prior therapy, and those who were refractory to Fludara or Campath were excluded. FluCAM patients received Campath in escalating doses of 3, 10, and 30 mg IV. The patients then received Fludara at 30 mg/m2 IV followed by Campath at 30 mg IV every 28 days for up to six cycles. Patients in the Fludara arm received Fludara at 25 mg/m2 IV daily for five consecutive days every 28 days for up to six cycles.
Campath is a humanized mAb that binds to CD52 on cell surfaces and directs the body’s immune system to destroy those cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell CLL. Fludara, a purine nucleotide analog, inhibits the synthesis of new DNA, thus preventing leukemia cells from multiplying.