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

Abstract

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/m2 BBR 2278 for a q1w x3 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/m2 BBR 2778 in a q1w x 3 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 for the treatment of NHL.

• Authors: Peter Borchmann, Franck Morschhauser, Anne Parry, Roland Schnell, Jean Luc Harousseau, Christian Gisselbrecht, Christian Rudolph, Martin Wilhelm, Hans Günther, Derigs Michael Pfreundschuh, Gabriella Camboni, Andreas Engert
• Journal: Haematologica (Haematologica) Vol. 88 Issue 8 Pg. 888-94 (Aug 2003) ISSN: 1592-8721 [Electronic] Italy
• PMID: 12935976 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Isoquinolines
• Topoisomerase II Inhibitors
• pixantrone

Topics

• Adult
• Aged
• Aged, 80 and over
• Anemia (chemically induced)
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Female
• Humans
• Isoquinolines (administration & dosage, adverse effects, therapeutic use)
• Lymphoma, Non-Hodgkin (blood, drug therapy, enzymology, pathology)
• Lymphopenia (chemically induced)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Neutropenia (chemically induced)
• Recurrence
• Thrombocytopenia (chemically induced)
• Topoisomerase II Inhibitors
• Treatment Outcome