Open AccessPhase I study of anti‐ CD 22 immunoconjugate inotuzumab ozogamicin plus rituximab in relapsed/refractory B ‐cell non‐ H odgkin lymphoma
Author(s) -
Ogura Michinori,
Hatake Kiyohiko,
Ando Kiyoshi,
Tobinai Kensei,
Tokushige Kota,
Ono Chiho,
Ishibashi Taro,
Vandendries Erik
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02241.x
Subject(s) - calicheamicin , medicine , rituximab , cd22 , neutropenia , tolerability , adverse effect , leukopenia , lymphoma , gastroenterology , refractory (planetary science) , phases of clinical research , febrile neutropenia , oncology , pharmacology , chemotherapy , cd20 , physics , myeloid leukemia , astrobiology
Inotuzumab ozogamicin ( CMC ‐544), a humanized anti‐ CD 22 antibody conjugated to the potent cytotoxic antibiotic calicheamicin, targets the CD 22 antigen expressed on the majority of B ‐cell non‐ H odgkin lymphomas. This phase I study assessed the tolerability, safety, pharmacokinetics, and preliminary efficacy of inotuzumab ozogamicin administered intravenously in combination with rituximab in Japanese patients with relapsed or refractory B ‐cell non‐ H odgkin lymphoma. Ten patients were administered rituximab 375 mg/m 2 followed by inotuzumab ozogamicin at the maximum tolerated dose (1.8 mg/m 2 ). Treatment was repeated every 28 days up to eight cycles, or until occurrence of disease progression or intolerable toxicity. The safety profile was similar to that of inotuzumab ozogamicin monotherapy, with hematologic adverse events occurring most frequently. The most common grade three or higher adverse events were thrombocytopenia (70%), neutropenia (50%), leukopenia (30%), and lymphopenia (30%). The overall response rate was 80% (8/10; 95% CI , 44–98%). Drug exposure increased with successive doses, similar to the pharmacokinetic profiles observed in previous phase I monotherapy studies. Efficacy results suggested promising antitumor activity, and the overall findings support the continued clinical development of this therapeutic regimen in patients with relapsed or refractory B ‐cell non‐ H odgkin lymphoma. This trial was registered at www.ClinicalTrials.gov as NCT 00724971. ( Cancer Sci 2012; 103: 933–938)