title: Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma.
abstract: OBJECTIVE
  To evaluate the safety, preliminary efficacy, and pharmacokinetics of inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, in combination with the immunochemotherapeutic regimen, rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), in patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma (NHL).
  
  
  METHODS
  In part 1 (n = 16), patients received inotuzumab ozogamicin plus R-CVP on a 21-day cycle with escalating doses of cyclophosphamide first then inotuzumab ozogamicin. Part 2 (n = 10) confirmed the safety and tolerability of the maximum tolerated dose (MTD), which required a dose-limiting toxicity rate of <33% in cycle 1 and <33% of patients discontinuing before cycle 3 due to treatment-related adverse events (AEs). Part 3 (n = 22) evaluated the preliminary efficacy of inotuzumab ozogamicin plus R-CVP.
  
  
  RESULTS
  The MTD was determined to be standard-dose R-CVP plus inotuzumab ozogamicin 0.8 mg/m2The most common treatment-related grade ≥3 AEs in the MTD cohort (n = 38) were hematologic: neutropenia (74%), thrombocytopenia (50%), lymphopenia (42%), and leukopenia (47%). Among the 48 patients treated in the study, 13 discontinued due to AEs, most commonly thrombocytopenia (n = 10). Overall, 13 patients died, including one death due to treatment-related pneumonia secondary to neutropenia. Among patients receiving the MTD (n = 38), the overall response rate (ORR) was 84% (n = 32), including 24% (n = 9) with complete response; the ORR was 100% for patients with indolent lymphoma (n = 27) and 57% for those with aggressive histology lymphoma (n = 21).
  
  
  CONCLUSIONS
  Inotuzumab ozogamicin at 0.8 mg/m2plus full dose R-CVP was associated with manageable toxicities and demonstrated a high rate of response in patients with relapsed/refractory CD22+ B-cell NHL. The study is registered at ClinicalTrials.gov (NCT01055496). Clin Cancer Res; 22(19); 4807-16. ©2016 AACR.
authors.affiliation: Nagoya Daini Red Cross Hospital, Nagoya, Japan. mi-ogura@naa.att.ne.jp.
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.affiliation: National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.affiliation: Cancer Institute Hospital, Tokyo, Japan.
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
authors.affiliation: Cancer Sciences Division, Somers Cancer Research Building, University of Southampton, Southampton, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.affiliation: Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Crump
authors.affiliation: Inventiv Health, Cambridge, Massachusetts.
authors.forename: Revathi
authors.initials: R
authors.lastname: Ananthakrishnan
authors.affiliation: Pfizer Japan, Tokyo, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Pfizer Inc, Groton, Conneticut.
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Paccagnella
authors.affiliation: Pfizer Inc, Collegeville, Pennsylvania.
authors.forename: Joseph
authors.initials: J
authors.lastname: Boni
authors.affiliation: Pfizer Inc, Cambridge, Massachusetts.
authors.forename: Erik
authors.initials: E
authors.lastname: Vandendries
authors.affiliation: Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: MacDonald
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000080045:Inotuzumab Ozogamicin; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C497867:CD22 protein, human; D051918:Sialic Acid Binding Ig-like Lectin 2; D000069283:Rituximab; D014750:Vincristine; D003520:Cyclophosphamide; D000080045:Inotuzumab Ozogamicin; D011241:Prednisone