演題詳細

ポスター / Poster

ポスター 9 (Poster 9) :CML:臨床1 (CML:Clinical Research 1)

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日程
2013年10月11日(金)
時間
16:50 - 17:50
会場
ポスター会場 / Poster (ロイトン札幌 3F ロイトンホールABCD)
座長・司会
田中 英夫 (Hideo Tanaka):1
1:広島市立安佐市民病院 血液内科
 
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Preliminary report of a phase 1/2 study of ponatinib in Japanese patients with Ph+ Leukemias

演題番号 : PS-1-61

Tetsuzo Tauchi:1、Arinobu Tojo:2、中前 博久 (Hirohisa Nakamae):3、小林 幸夫 (Yukio Kobayashi):4、Shinichiro Okamoto:5、宮村 耕一 (Koichi Miyamura):6、許 泰一 (Taiichi Kyo):7、岩崎 浩己 (Hiromi Iwasaki):8、畠 清彦 (Kiyohiko Hatake):9、Noriko Usui:10、Narayana I Narasimhan:11、Simin Hu:11、Kumiko Yanase:11、Joshua Zhang:11、直江 知樹 (Tomoki Naoe):12、Kazuma Ohyashiki:1

1:Tokyo Medical University Hospital, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan、2:The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan、3:Osaka City University Hospital, Osaka City University, Osaka-shi, Osaka, Japan、4:National Cancer Center Hospital, Chuo-ku, Tokyo, Japan、5:Keio University Hospital, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan、6:Japan Red Cross Nagoya Daiichi Hospital, Nagoya-shi, Aichi, Japan、7:Hiroshima Red Cross and Atomic Bomb Survivors Hospital, Naka-ku, Hiroshima, Japan、8:Kyushu University Hospital, Kyushu University, Higashi-ku Fukuoka, Japan、9:Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan、10:Jikei University Daisan Hospital, Komae-shi, Tokyo, Japan、11:ARIAD Pharmaceuticals, Inc., Cambridge, MA, USA、12:Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan

 

Background: Ponatinib is an FDA-approved, potent oral pan–BCR-ABL tyrosine kinase inhibitor (TKI) that is active against native and mutated forms of BCR-ABL, including T315I. This is the first study of ponatinib in Japanese pts with chronic myeloid leukemia (CML) resistant/intolerant (R/I) to dasatinib or nilotinib, or with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) R/I to prior TKIs. Methods: In the dose-escalation phase (modified 3+3 design), 2 dose levels of once-daily ponatinib (30 mg n=6; 45 mg n=6) are being evaluated to examine the safety of the dose recommended for further study in Japan (45 mg) and to determine the recommended phase 2 dose (RP2D) via dose-limiting toxicity (DLT) evaluation. Efficacy will also be assessed. Overall, approximately 15 pts with chronic phase (CP) CML and 8 pts each with accelerated phase (AP) or blast phase (BP) CML, or Ph+ ALL, will be enrolled. Updated data and the RP2D will be presented.Results: As of 4 March 2013, 12 pts were enrolled; 67% male; median age was 60 (30–70) yrs; median time since diagnosis was 3 (0.5–21) yrs; 92% received ≥2 prior TKIs. Diagnoses were 4 CP-CML, 2 AP-CML, 1 BP- CML, and 5 Ph+ ALL. One DLT was observed at 30 mg in a Ph+ ALL pt (Grade 5 liver failure). No other DLTs occurred, allowing for dose escalation to the 45 mg dose level, which remains under evaluation for DLTs. The most common treatment-related adverse events (n=2 each) were pyrexia and elevated levels of ALT, AST, gamma glutamyltransferase, and lipase. Day 29 PK (30 mg n=5): geometric mean Cmax=53.4 ng/mL, Ctrough=25.8 ng/mL, AUC0-24=969.4 ng*hr/mL, t1/2=18.2 hr.Conclusions: Ponatinib was generally well-tolerated in heavily pretreated Japanese pts. The 30-mg PK profile was consistent with that observed in a Western population. Phase 2 will begin after the RP2D is determined. ClinicalTrials.gov ID: NCT0166713

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