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

Haematologica. 2003 Aug;88(8):888-94.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

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

Substances

  • Antineoplastic Agents
  • Isoquinolines
  • Topoisomerase II Inhibitors
  • pixantrone