title: Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy.
abstract: 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).
authors.affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan. mi-ogura@naa.att.ne.jp
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kasai
authors.forename: Takashi
authors.initials: T
authors.lastname: Oyama
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Teruhisa
authors.initials: T
authors.lastname: Azuma
authors.forename: Masakazu
authors.initials: M
authors.lastname: Mori
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Terui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mishima
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Chiho
authors.initials: C
authors.lastname: Ono
authors.forename: Junko
authors.initials: J
authors.lastname: Ohata
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D000080045:Inotuzumab Ozogamicin