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


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.


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.
Borchmann
Peter
P
Klinik I für Innere Medizin der Universität zu Köln, Germany.
Morschhauser
Franck
F
Parry
Anne
A
Schnell
Roland
R
Harousseau
Jean Luc
JL
Gisselbrecht
Christian
C
Rudolph
Christian
C
Wilhelm
Martin
M
Günther
Hans
H
Pfreundschuh
Derigs Michael
DM
Camboni
Gabriella
G
Engert
Andreas
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D013921:Thrombocytopenia / Q000139:chemically induced; D059005:Topoisomerase II Inhibitors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D007546:Isoquinolines; D059005:Topoisomerase II Inhibitors; C086548:pixantrone