PMID- 33728735
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20210616
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 112
IP  - 6
DP  - 2021 Jun
TI  - Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell 
      malignancies: A Japanese phase I study.
PG  - 2405-2415
LID - 10.1111/cas.14886 [doi]
AB  - This multicenter, open-label, phase I study assessed the safety and antitumor 
      activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) 
      B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this 
      three-part study are reported. Treatment was a single dose of 100 mg 
      acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg 
      acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients 
      from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic 
      lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL 
      and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 
      1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two 
      patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL 
      cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of 
      patients (grade >/=3, 36%); the most common were headache (28%) and purpura (24%), 
      both grade 1/2. No AEs resulted in treatment discontinuation or death. Median 
      duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, 
      and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for 
      the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free 
      survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for 
      the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and 
      well-tolerated in adult Japanese patients with B-cell malignancies.
CI  - (c) 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Izutsu, Koji
AU  - Izutsu K
AUID- ORCID: 0000-0001-9129-8057
AD  - National Cancer Center Hospital, Tokyo, Japan.
FAU - Ando, Kiyoshi
AU  - Ando K
AD  - Tokai University Hospital, Isehara, Japan.
FAU - Ennishi, Daisuke
AU  - Ennishi D
AD  - Okayama University Hospital, Okayama, Japan.
FAU - Shibayama, Hirohiko
AU  - Shibayama H
AUID- ORCID: 0000-0003-4014-2815
AD  - Osaka University Hospital, Osaka, Japan.
FAU - Suzumiya, Junji
AU  - Suzumiya J
AD  - Shimane University Hospital, Izumo, Japan.
FAU - Yamamoto, Kazuhito
AU  - Yamamoto K
AUID- ORCID: 0000-0002-8588-8955
AD  - Aichi Cancer Center Hospital, Nagoya, Japan.
FAU - Ichikawa, Satoshi
AU  - Ichikawa S
AUID- ORCID: 0000-0003-3163-7197
AD  - Tohoku University Hospital, Sendai, Japan.
FAU - Kato, Koji
AU  - Kato K
AUID- ORCID: 0000-0002-5815-4585
AD  - Kyushu University Hospital, Fukuoka, Japan.
FAU - Kumagai, Kyoya
AU  - Kumagai K
AD  - Chiba Cancer Center, Chiba, Japan.
FAU - Patel, Priti
AU  - Patel P
AD  - Acerta Pharma, South San Francisco, CA, USA.
FAU - Iizumi, Sakura
AU  - Iizumi S
AUID- ORCID: 0000-0001-6760-152X
AD  - AstraZeneca K.K., Tokyo, Japan.
FAU - Hayashi, Nobuya
AU  - Hayashi N
AUID- ORCID: 0000-0002-5386-5599
AD  - AstraZeneca K.K, Osaka, Japan.
FAU - Kawasumi, Hisashi
AU  - Kawasumi H
AUID- ORCID: 0000-0002-5981-2383
AD  - AstraZeneca K.K., Tokyo, Japan.
FAU - Murayama, Kosho
AU  - Murayama K
AUID- ORCID: 0000-0003-3301-9966
AD  - AstraZeneca K.K, Osaka, Japan.
FAU - Nagai, Hirokazu
AU  - Nagai H
AD  - National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
LA  - eng
GR  - AstraZeneca/
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20210507
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Pyrazines)
RN  - I42748ELQW (acalabrutinib)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Benzamides/*administration & dosage/adverse effects/pharmacokinetics
MH  - Drug Administration Schedule
MH  - Female
MH  - Headache/chemically induced/epidemiology
MH  - Humans
MH  - Japan
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/blood/*drug therapy
MH  - Lymphoma, Mantle-Cell/blood/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/blood/*drug therapy
MH  - Purpura/chemically induced/epidemiology
MH  - Pyrazines/*administration & dosage/adverse effects/pharmacokinetics
MH  - Survival Analysis
MH  - Treatment Outcome
PMC - PMC8177795
OTO - NOTNLM
OT  - Bruton's tyrosine kinase
OT  - chronic lymphocytic leukemia
OT  - mantle cell lymphoma
OT  - pharmacokinetics
OT  - small lymphocytic lymphoma
COIS- Koji Izutsu has received research funds from AstraZeneca. Kiyoshi Ando has 
      received research funds from AstraZeneca. Daisuke Ennishi has no conflict of 
      interest to declare. Hirohiko Shibayama has received honoraria from Takeda, 
      Novartis, Celgene, Janssen, Chugai, and Kyowa Kirin; research funds from Janssen, 
      Ono, Celgene, Novartis, Sanofi, AstraZeneca, AbbVie, and Chugai; and scholarships 
      from Astellas, Teijin, Shionogi, Eisai, Sanofi, Taiho, and Nippon Shinyaku. Junji 
      Suzumiya has received honoraria from AstraZeneca, AbbVie, Bristol Myers Squibb, 
      Celgene, Chugai, Eisai, Janssen, and Takeda; and research funds from AstraZeneca, 
      Bayer, Celgene, Chugai, Eisai, Kyowa Kirin, Ono, SymBio, Takeda, and Yakult. 
      Kazuhito Yamamoto has received honoraria from Chugai, Eisai, HUYA/IQVIA, 
      Mundipharma, and Takeda; and research funds from AbbVie, AstraZeneca, Bayer, 
      Celgene, Chugai, Eisai, Incyte/IQVIA, Mundipharma, Nippon Shinyaku, Novartis, 
      Solasia Pharma, SymBio, Yakult, and Zenyaku Kogyo. Satoshi Ichikawa has received 
      research funds from Chugai. Koji Kato has received honoraria from Novartis, 
      Eisai, Janssen, Celgene, Takeda, MSD, Kyowa Kirin, Janssen, Celgene, Ono, 
      Mundipharma, and Sumitomo Dainippon; and research funds from Chugai, Takeda, 
      Kyowa Kirin, AbbVie, Novartis, Eisai, Janssen, Celgene, and Ono. Kyoya Kumagai 
      has no conflict of interest to declare. Priti Patel is employed by Acerta Pharma. 
      Sakura Iizumi, Nobuya Hayashi, Hisashi Kawasumi, and Kosho Murayama are employed 
      by AstraZeneca. Hirokazu Nagai has received honoraria from Celgene, Takeda, 
      Eisai, Chugai, and Mundipharma; research funds from Bayer, AstraZeneca, Zenyaku 
      Kogyo, Takeda, Mundipharma, SymBio, and Chugai; and scholarships from Chugai.
EDAT- 2021/03/18 06:00
MHDA- 2021/06/11 06:00
PMCR- 2021/06/01
CRDT- 2021/03/17 07:11
PHST- 2021/03/12 00:00 [revised]
PHST- 2020/12/21 00:00 [received]
PHST- 2021/03/15 00:00 [accepted]
PHST- 2021/03/18 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2021/03/17 07:11 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - CAS14886 [pii]
AID - 10.1111/cas.14886 [doi]
PST - ppublish
SO  - Cancer Sci. 2021 Jun;112(6):2405-2415. doi: 10.1111/cas.14886. Epub 2021 May 7.