PMID- 27154915
OWN - NLM
STAT- MEDLINE
DCOM- 20180105
LR  - 20191210
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 22
IP  - 19
DP  - 2016 Oct 1
TI  - Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for 
      Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma.
PG  - 4807-4816
AB  - PURPOSE: 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). EXPERIMENTAL DESIGN: 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/m(2) The 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/m(2) plus 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. (c)2016 AACR.
CI  - (c)2016 American Association for Cancer Research.
FAU - Ogura, Michinori
AU  - Ogura M
AD  - Nagoya Daini Red Cross Hospital, Nagoya, Japan. mi-ogura@naa.att.ne.jp.
FAU - Tobinai, Kensei
AU  - Tobinai K
AD  - National Cancer Center Hospital, Tokyo, Japan.
FAU - Hatake, Kiyohiko
AU  - Hatake K
AD  - Cancer Institute Hospital, Tokyo, Japan.
FAU - Davies, Andrew
AU  - Davies A
AD  - Cancer Sciences Division, Somers Cancer Research Building, University of 
      Southampton, Southampton, United Kingdom.
FAU - Crump, Michael
AU  - Crump M
AD  - Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
FAU - Ananthakrishnan, Revathi
AU  - Ananthakrishnan R
AD  - Inventiv Health, Cambridge, Massachusetts.
FAU - Ishibashi, Taro
AU  - Ishibashi T
AD  - Pfizer Japan, Tokyo, Japan.
FAU - Paccagnella, M Luisa
AU  - Paccagnella ML
AD  - Pfizer Inc, Groton, Conneticut.
FAU - Boni, Joseph
AU  - Boni J
AD  - Pfizer Inc, Collegeville, Pennsylvania.
FAU - Vandendries, Erik
AU  - Vandendries E
AD  - Pfizer Inc, Cambridge, Massachusetts.
FAU - MacDonald, David
AU  - MacDonald D
AD  - Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada.
LA  - eng
SI  - ClinicalTrials.gov/NCT01055496
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20160506
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CD22 protein, human)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 2)
RN  - 4F4X42SYQ6 (Rituximab)
RN  - 5J49Q6B70F (Vincristine)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - P93RUU11P7 (Inotuzumab Ozogamicin)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Cyclophosphamide/therapeutic use
MH  - Female
MH  - Humans
MH  - Inotuzumab Ozogamicin
MH  - Lymphoma, B-Cell/*drug therapy
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy
MH  - Prednisone/therapeutic use
MH  - Rituximab/therapeutic use
MH  - Sialic Acid Binding Ig-like Lectin 2
MH  - Vincristine/therapeutic use
EDAT- 2016/05/08 06:00
MHDA- 2018/01/06 06:00
CRDT- 2016/05/08 06:00
PHST- 2015/10/13 00:00 [received]
PHST- 2016/04/13 00:00 [accepted]
PHST- 2016/05/08 06:00 [pubmed]
PHST- 2018/01/06 06:00 [medline]
PHST- 2016/05/08 06:00 [entrez]
AID - 1078-0432.CCR-15-2488 [pii]
AID - 10.1158/1078-0432.CCR-15-2488 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2016 Oct 1;22(19):4807-4816. doi: 10.1158/1078-0432.CCR-15-2488. 
      Epub 2016 May 6.