Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia.
OBJECTIVE
The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL.


METHODS
Patients younger than age 19 years with CD20(+) B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m(2) administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had > or = 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity.


RESULTS
From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007).


CONCLUSIONS
Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.
Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Münster Study Center, Justus Liebig University Giessen, Giessen, Germany.
Andrea
A
Meinhardt
Birgit
B
Burkhardt
Martin
M
Zimmermann
Arndt
A
Borkhardt
Udo
U
Kontny
Thomas
T
Klingebiel
Frank
F
Berthold
Gritta
G
Janka-Schaub
Christoph
C
Klein
Edita
E
Kabickova
Wolfram
W
Klapper
Andishe
A
Attarbaschi
Martin
M
Schrappe
Alfred
A
Reiter
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D009325:Nausea / Q000139:chemically induced; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab