Preliminary Phase II Study Results of BBR2778 in Combination with Cyclophosphamide, Vincristine, and Prednisone in Patients with Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Background: Pixantrone (BBR 2778) is a novel aza-anthracenedione with superior activity compared to doxorubicin and mitoxantrone in various tumor models including hematological malignancies. Pixantrone single agent therapy led to major responses in patients (pts) with aggressive lymphoma including diffuse large B-cell lymphoma (DLCL). The safety of a CHOP-like regimen with pixantrone replacing doxorubicin (CPOP) was assessed in a dose-ranging study indicating a recommended dose of 150 mg/m² for pixantrone.

Method: In this phase II study the primary objective was to assess the efficacy of the CPOP regimen (cyclophosphamide 750 mg/m² d1, pixantrone 150mg/m² d1, vincristine 1.4mg/m² d1, limited to 2mg, and prednisone 100mg d1 to 5) in pts with relapsed DLCL, transformed follicular lymphoma (tFL) and mantle cell lymphoma (MCL) for a total of 6 cycles given every 3 weeks. Hematopoietic growth factors were not permitted for the first cycle and used thereafter according to the ASCO guidelines. Inclusion/exclusion criteria included at least one but not more than two previous chemotherapy lines containing an anthracycline/anthracenedione with a cumulative dose of less than 450mg/m² doxorubicin equivalent, a left ventricular ejection fraction (LVEF) >50%, no meningeal involvement, and HIV negative serology.

Results: 21 pts have currently been included. Data is available for the first 15 pts. Main baseline characteristics are: median age 65 y [35 – 76]; DLCL 10 cases, tFL 2 cases, MCL 3 cases; stage I/II 4 cases, stage III/IV 11 cases; median number of previous therapy lines 2 [1–5], median prior cumulative dose of anthracyclines 320 mg/m² [104 – 452 mg/m²]. 48 cycles of CPOP have been administered to date, with a median number of 4 per pt. Most common grade 3 or 4 adverse events were neutropenia [39 episodes in 10 (67%) pts], leucopenia [37 episodes in 10 (67%) pts], thrombocytopenia [3 episodes in 3 (20%) pts] and febrile neutropenia [8 episodes in 4 (27%) pts]. There was no treatment related death and no grade 3 or 4 organ toxicity. Treatment was delayed in 6 pts and the doses of pixantrone and cyclophosphamide were reduced in 5 pts for a grade 4 hematological toxicity or infection. Only one patient had a decrease of ≥10% of LVEF from 72% at screening to 56% after 6 cycles without clinical symptoms. Out of 12 pts currently evaluable for response, 6 (50%) responded to CPOP therapy: 5 CR and 1 PR (responses maintained for ≥8 weeks).

Conclusion : These early results of the CPOP regimen with 150 mg/m² of pixantrone indicates a high response rate in pts with relapsed aggressive B cell lymphoma with an acceptable and manageable safety profile.