Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy.
Inotuzumab ozogamicin (CMC-544), an antibody-targeted chemotherapeutic agent composed of an anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic antibiotic, specifically targets the CD22 antigen present in >90% of B-lymphoid malignancies, rendering it useful for treating patients with B-cell non-Hodgkin lymphoma (B-NHL). This phase I study evaluated the safety, tolerability, efficacy, and pharmacokinetics of inotuzumab ozogamicin in Japanese patients. Eligible patients had relapsed or refractory CD22-positive B-NHL without major organ dysfunction. Inotuzumab ozogamicin was administered intravenously once every 28 days (dose escalation: 1.3 and 1.8 mg/m(2)). All 13 patients had follicular lymphoma, were previously treated with > or =1 rituximab-alone or rituximab-containing chemotherapy, and were enrolled into two dose cohorts (1.3 mg/m(2), three patients; 1.8 mg/m(2), 10 patients). No patient had dose-limiting toxicities, and the maximum tolerated dose, previously determined in non-Japanese patients (1.8 mg/m(2)), was confirmed. Drug-related adverse events (AEs) included thrombocytopenia (100%), leukopenia (92%), lymphopenia (85%), neutropenia (85%), elevated AST (85%), anorexia (85%), and nausea (77%). Grade 3/4 drug-related AEs in > or =15% patients were thrombocytopenia (54%), lymphopenia (31%), neutropenia (31%), and leukopenia (15%). The AUC and C(max) of inotuzumab ozogamicin increased dose-dependently with pharmacokinetic profiles similar to non-Japanese. Seven patients had complete response (CR, 54%) including unconfirmed CR, four patients had partial response (31%), and two patients had stable disease (15%). The overall response rate was 85% (11/13). Inotuzumab ozogamicin was well tolerated at doses up to 1.8 mg/m(2) and showed preliminary evidence of activity in relapsed or refractory follicular lymphoma pretreated with rituximab-containing therapy, warranting further investigations. This trial was registered in ClinicalTrials.gov (NCT00717925).
Ogura
Michinori
M
Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan. mi-ogura@naa.att.ne.jp
Tobinai
Kensei
K
Hatake
Kiyohiko
K
Uchida
Toshiki
T
Kasai
Masanobu
M
Oyama
Takashi
T
Suzuki
Tatsuya
T
Kobayashi
Yukio
Y
Watanabe
Takashi
T
Azuma
Teruhisa
T
Mori
Masakazu
M
Terui
Yasuhito
Y
Yokoyama
Masahiro
M
Mishima
Yuko
Y
Takahashi
Shunji
S
Ono
Chiho
C
Ohata
Junko
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D008224:Lymphoma, Follicular / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D000080045:Inotuzumab Ozogamicin