PMID- 35635686
OWN - NLM
STAT- MEDLINE
DCOM- 20220929
LR  - 20230321
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 116
IP  - 4
DP  - 2022 Oct
TI  - A phase I study of inotuzumab ozogamicin as a single agent in pediatric patients 
      in Japan with relapsed/refractory CD22-positive acute lymphoblastic leukemia 
      (INO-Ped-ALL-1).
PG  - 612-621
LID - 10.1007/s12185-022-03388-8 [doi]
AB  - Inotuzumab ozogamicin (InO) is a CD22-directed antibody conjugated with 
      calicheamicin approved for adult relapsed or refractory CD22-positive acute 
      lymphoblastic leukemia (ALL). This phase 1 study primarily aimed to determine the 
      pediatric recommended doses of InO through the standard 3 + 3 design, and to 
      evaluate the safety, tolerability, pharmacokinetic (PK) profile, immunogenicity 
      and efficacy of InO. Dose level 1 (DL1) was 1.8 mg/m(2) (days 1, 8, and 15: 0.8, 
      0.5, and 0.5 mg/m(2), respectively). Six of the seven registered patients were 
      eligible [median age, 7.5 (2-17) years]. Although all six patients started DL1, 
      only five completed the dose. No dose-limiting toxicity was observed. All 
      patients experienced adverse events (AEs), including increased alanine 
      aminotransferase and aspartate aminotransferase in four patients. Three patients 
      experienced serious AEs, which were hepatic veno-occlusive disease (VOD), ALL, 
      and fever. Five patients achieved complete remission (CR) or CR with incomplete 
      blood cell recovery (CRi), among whom 3 (60%) were negative for minimal residual 
      disease. PK findings were similar to those in adults. No patient had anti-drug 
      antibodies to InO. In conclusion, InO was well tolerated in children and promoted 
      similar antileukemic efficacy as in adults. Nonetheless, the risk for VOD 
      requires attention.
CI  - (c) 2022. Japanese Society of Hematology.
FAU - Nakayama, Hideki
AU  - Nakayama H
AUID- ORCID: 0000-0002-1994-113X
AD  - Department of Pediatrics, National Hospital Organization Kyushu Cancer Center, 
      Fukuoka, Japan. hnkym415@gmail.com.
FAU - Ogawa, Chitose
AU  - Ogawa C
AD  - Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan.
FAU - Sekimizu, Masahiro
AU  - Sekimizu M
AD  - Clinical Research Center, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
AD  - Department of Pediatrics, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
FAU - Fujisaki, Hiroyuki
AU  - Fujisaki H
AD  - Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, 
      Japan.
FAU - Kosaka, Yoshiyuki
AU  - Kosaka Y
AD  - Department of Hematology and Oncology, Hyogo Prefectural Kobe Children's 
      Hospital, Kobe, Japan.
FAU - Hashimoto, Hiroya
AU  - Hashimoto H
AD  - Clinical Research Center, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
AD  - Core Laboratory, Graduate School of Medical Sciences, Nagoya City University, 
      Nagoya, Japan.
FAU - Saito, Akiko M
AU  - Saito AM
AD  - Clinical Research Center, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
FAU - Horibe, Keizo
AU  - Horibe K
AD  - Clinical Research Center, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
AD  - Department of Pediatrics, National Hospital Organization Nagoya Medical Center, 
      Nagoya, Japan.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20220530
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (CD22 protein, human)
RN  - 0 (Calicheamicins)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 2)
RN  - EC 2.6.1.1 (Aspartate Aminotransferases)
RN  - EC 2.6.1.2 (Alanine Transaminase)
RN  - P93RUU11P7 (Inotuzumab Ozogamicin)
SB  - IM
EIN - Int J Hematol. 2023 May;117(5):786. PMID: 36943610
MH  - Adolescent
MH  - Alanine Transaminase
MH  - Aspartate Aminotransferases
MH  - *Calicheamicins
MH  - Child
MH  - Child, Preschool
MH  - Humans
MH  - Inotuzumab Ozogamicin
MH  - Japan
MH  - *Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
MH  - Sialic Acid Binding Ig-like Lectin 2/therapeutic use
OTO - NOTNLM
OT  - Acute lymphoblastic leukemia
OT  - CD22
OT  - Children
OT  - Inotuzumab ozogamicin
OT  - Relapse/refractory
EDAT- 2022/06/01 06:00
MHDA- 2022/09/30 06:00
CRDT- 2022/05/31 12:45
PHST- 2022/02/14 00:00 [received]
PHST- 2022/05/10 00:00 [accepted]
PHST- 2022/05/09 00:00 [revised]
PHST- 2022/06/01 06:00 [pubmed]
PHST- 2022/09/30 06:00 [medline]
PHST- 2022/05/31 12:45 [entrez]
AID - 10.1007/s12185-022-03388-8 [pii]
AID - 10.1007/s12185-022-03388-8 [doi]
PST - ppublish
SO  - Int J Hematol. 2022 Oct;116(4):612-621. doi: 10.1007/s12185-022-03388-8. Epub 
      2022 May 30.