The Phase I/IIa multi-center dose-escalation study was designed to assess the safety, efficacy and pharmacokinetics of Acadra® in CLL patients with refractory or relapsed disease.
The results of this study demonstrated that Acadra® has an acceptable safety and tolerability profile at doses that induce reduction in the leukemic tumor burden. The study patient population included patients with relapsed or refractory CLL who had received a minimum of one prior line of treatment including either a fludarabine or an alkylator-based regimen (median number of prior treatments was 5). The study was conducted in two parts and enrolled twenty-four patients in cohorts of 3 patients each.
The study was closely followed by a Data Monitoring Board formed by four independent CLL international experts that concluded that "Although the study was not designed to analyze peripheral blood response and lymph node response, clear evidence of efficacy has been obtained to move forward. The good safety profile of Acadra® observed makes it an attractive combination partner with other CLL therapies."
In addition to the clinical results in the CLL phase I/IIa study, Advancell has conducted in vivo non-clinical studies in other lymphoproliferative disorders. These studies have demonstrated that Acadra® has anticancer activity in both Multiple Myeloma and Mantle Cell Lymphoma with Acadra® doses equivalent to those that have shown to be safe and well tolerated in the CLL clinical trial. Interestingly, the drug has demonstrated synergic effects in combination with bortezomib in a Multiple Myeloma animal model and in combination with rituximab in a p53-mutated Mantle Cell Lymphoma animal model. These results suggest a potential use of Acadra® as part of combination therapy in these indications.