Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma

Background: BBR 2778 is a novel aza-anthracenedione showing no cardiotoxici ty and superior activity compared to doxorubicin and mitoxantrone in animal models. Objectives of this phase I study included the determination of the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), clinical p harmacokinetics (PK), and antitumor activity. Patients with relapsed or ref ractory, advanced non-Hodgkin's lymphoma were included. Patients and methods: Patients were treated with a q1w x 3 schedule on the basis of a modified Fibonacci dose escalation method. Seven groups with a t otal of twenty-six patients were treated at dosages of 5, 10, 16.5, 25, 34, 56 or 84 mg/m(2)/w, respectively. Results: DLT was observed on the seventh dose level with neutropenia WHO gr ade 4 in three of six patients. Pharmacokinetic analysis showed a large vol ume of distribution (13.5-17.5 l/kg), a high plasma clearance (0.65-1.74 l/ h/kg) and a long elimination half-life (14.7-31.9 h). Tumor response includ ed three complete remissions and two partial remissions. Conclusions: Neutropenia is the DLT of the new aza-anthracenedione BBR 2778 . The recommend dose is 84 mg/m(2) in a q1w x 3 schedule. PK data are consi stent with a linear kinetic of BBR 2778 comparable to mitoxantrone. This ne w drug shows promising activity in intensively pretreated patients with rel apsed or refractory NHL. Based on this results, phase II studies with this new compound are underway.