Phase-II study of the new aza-anthracenedione, BBR 2778, in patients with relapsed aggressive non-Hodgkin's lymphomas

Background and Objectives. BBR 2778 is a new aza-anthracenedione. Its activity against hematologic neoplasias in a mouse model is greater than that of doxorubicin or mitoxantrone. A phase-I study in patients with non-Hodgkin's lymphoma (NHL) showed that the drug has promising anti-tumor activity. Therefore, a phase-II study in patients with relapsed aggressive NHL was initiated. Design and Methods. the primary objective was to determine the efficacy of 85 mg/m(2) BBR 2278 for a q1w x 3 treatment schedule (repeat day 29). Secondary objectives included the evaluation of response duration and safety in this open-label, non-randomized, multicenter trial. Patients with relapsed aggressive NHL according to the REAL classification were included. Results. Eight centers enrolled a total of 33 patients. The median age of these patients was 66 years (range 24-81). The majority of patients had diffuse large B-cell lymphoma (n = 24) or mantle-cell lymphoma (n = 7), pretreated with a median of 2 regimens. Confirmed responses included 5 complete and 4 partial remissions, with the period between the first appearance of response and any signs or symptoms of progression being up to 17+ months. The main toxicity was neutropenia. Interpretations and Conclusions. These results indicate that 85 mg/m(2) BBR 2778 in a q1w x 4 schedule is active in elderly and pretreated patients with relapsed aggressive NHL and was generally well tolerated. Thus, we recommend further clinical evaluation of this new compound in phase-III studies of the treatment of NHL.