臨床研究等提出・公開システム
臨床研究・治験計画情報の詳細情報です。(Japic)
| 企業治験 | ||
| 主たる治験と拡大治験のいずれにも該当しない | ||
| 平成27年1月13日 | ||
| 令和6年2月27日 | ||
| 令和2年3月14日 | ||
| 新たに急性骨髄性白血病と診断された患者を対象としたulocuplumab（BMS-936564）／低用量シタラビン併用療法の非盲検ランダム化第1/2相臨床試験 | ||
| BMS-936564の第1/2相臨床試験 | ||
| ブリストル・マイヤーズ スクイブ株式会社 | ||
| 本試験の目的は新たに診断された急性骨髄性白血病患者を対象に、低用量シタラビンとの併用でulocuplumab(BMS-936564)の安全性及び有効性を評価することである。 | ||
| 1-2 | ||
| 急性骨髄性白血病 | ||
| 参加募集終了 | ||
| ulocuplumab(BMS-936564)、シタラビン、- | ||
| 東京都立駒込病院 治験審査委員会 | ||
総括報告書の概要
総括報告書の概要
管理的事項
管理的事項
| 2024年02月22日 | ||
２ 結果の要約
２ 結果の要約
| 2020年03月14日 | ||
| 104 | ||
| / | ULO 600 mg + LDAC - Ph1群: ulocuplumab 600 mg + 低用量シタラビン - 第1相試験 ULO 800 mg + LDAC - Ph1群: ulocuplumab 800 mg + 低用量シタラビン - 第1相試験 ULO 800 mg + LDAC - Ph2群: ulocuplumab 800 mg + 低用量シタラビン - 第2相試験 ULO 1000 mg + LDAC - Ph2群: ulocuplumab 1000 mg + 低用量シタラビン - 第2相試験 LDAC - Ph2群: 低用量シタラビン - 第2相試験 ベースラインにおける被験者数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例, 合計 - Ph1: 6例 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 24例, 合計 - Ph2: 64例 年齢の平均値 (標準偏差) ULO 600 mg + LDAC - Ph1群: 73.7歳 (8.02), ULO 800 mg + LDAC - Ph1群: 77.3歳 (1.53), 合計 - Ph1: 75.5歳 (5.54) ULO 800 mg + LDAC - Ph2群: 74.9歳 (5.4), ULO 1000 mg + LDAC - Ph2群: 73.1歳 (3.7), LDAC - Ph2群: 75.9歳 (5.7), 合計 - Ph2: 74.9歳 (5.2) 年齢区分, n (%) 第1相試験Escalationコホート < 65 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例, 合計 - Ph1: 0例 ≧ 65 - < 75 ULO 600 mg + LDAC - Ph1群: 2例 (66.7), ULO 800 mg + LDAC - Ph1群: 0例, 合計 - Ph1: 2例 (33.3) ≧ 75 ULO 600 mg + LDAC - Ph1群: 1例 (33.3), ULO 800 mg + LDAC - Ph1群: 3例 (100.0), 合計 - Ph1: 4例 (66.7) 第2相試験Expansionコホート < 70 ULO 800 mg + LDAC - Ph2群: 4例 (15.4), ULO 1000 mg + LDAC - Ph2群: 3例 (21.4), LDAC - Ph2群: 3例 (12.5), 合計 - Ph2: 10例 (15.6) ≧ 70 ULO 800 mg + LDAC - Ph2群: 22例 (84.6), ULO 1000 mg + LDAC - Ph2群: 11例 (78.6), LDAC - Ph2群: 21例 (87.5), 合計 - Ph2: 54例 (84.4) 性別, n (%) 女性 ULO 600 mg + LDAC - Ph1群: 3例 (100.0), ULO 800 mg + LDAC - Ph1群: 0例, 合計 - Ph1: 3例 (50.0) ULO 800 mg + LDAC - Ph2群: 9例 (34.6), ULO 1000 mg + LDAC - Ph2群: 7例 (50.0), LDAC - Ph2群: 14例 (58.3), 合計 - Ph2: 30例 (46.9) 男性 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 3例 (100.0), 合計 - Ph1: 3例 (50.0) ULO 800 mg + LDAC - Ph2群: 17例 (65.4), ULO 1000 mg + LDAC - Ph2群: 7例 (50.0), LDAC - Ph2群: 10例 (41.7), 合計 - Ph2: 34例 (53.1) 人種, n (%) 第1相試験Escalationコホート 日本人 ULO 600 mg + LDAC - Ph1群: 3例 (100.0), ULO 800 mg + LDAC - Ph1群: 3例 (100.0), 合計 - Ph1: 6例 (100.0) 第2相試験Expansionコホート 白人 ULO 800 mg + LDAC - Ph2群: 15例 (57.7), ULO 1000 mg + LDAC - Ph2群: 4例 (28.6), LDAC - Ph2群: 12例 (50.0), 合計 - Ph2: 31例 (48.4) 黒人/アフリカ系アメリカ人 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例, 合計 - Ph2: 0例 日本人 ULO 800 mg + LDAC - Ph2群: 6例 (23.1), ULO 1000 mg + LDAC - Ph2群: 6例 (42.9), LDAC - Ph2群: 4例 (16.7), 合計 - Ph2: 16例 (25.0) 中国人 ULO 800 mg + LDAC - Ph2群: 2例 (7.7), ULO 1000 mg + LDAC - Ph2群: 2例 (14.3), LDAC - Ph2群: 3例 (12.5), 合計 - Ph2: 7例 (10.9) アジア系インド人 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例, 合計 - Ph2: 0例 その他のアジア人 ULO 800 mg + LDAC - Ph2群: 3例 (11.5), ULO 1000 mg + LDAC - Ph2群: 0例 (0.0), LDAC - Ph2群: 2例 (8.3), 合計 - Ph2: 5例 (7.8) アメリカ先住民/アラスカ先住民 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例 (7.1), LDAC - Ph2群: 0例, 合計 - Ph2: 1例 (1.6) ハワイ先住民/その他の太平洋諸島の住民 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例, 合計 - Ph2: 0例 その他 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例 (7.1), LDAC - Ph2群: 3例 (12.5), 合計 - Ph2: 4例 (6.3) |
ULO 600 mg + LDAC - Ph1: ulocuplumab 600 mg + low dose cytarabine - Phase 1 ULO 800 mg + LDAC - Ph1: ulocuplumab 800 mg + low dose cytarabine - Phase 1 ULO 800 mg + LDAC - Ph2: ulocuplumab 800 mg + low dose cytarabine - Phase 2 ULO 1000 mg + LDAC - Ph2: ulocuplumab 1000 mg + low dose cytarabine - Phase 2 LDAC - Ph2: low dose cytarabine - Phase 2 Overall Number of Baseline Subjects, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3, Total - Ph1: 6 ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 24, Total - Ph2: 64 Age (years), Mean (Standard Deviation) ULO 600 mg + LDAC - Ph1: 73.7 (8.02), ULO 800 mg + LDAC - Ph1: 77.3 (1.53), Total - Ph1: 75.5 (5.54) ULO 800 mg + LDAC - Ph2: 74.9 (5.4), ULO 1000 mg + LDAC - Ph2: 73.1 (3.7), LDAC - Ph2: 75.9 (5.7), Total - Ph2: 74.9 (5.2) Age Categorization, n (%) Phase 1 Escalation Cohort < 65 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0, Total - Ph1: 0 >= 65 - < 75 ULO 600 mg + LDAC - Ph1: 2 (66.7), ULO 800 mg + LDAC - Ph1: 0, Total - Ph1: 2 (33.3) >= 75 ULO 600 mg + LDAC - Ph1: 1 (33.3), ULO 800 mg + LDAC - Ph1: 3 (100.0), Total - Ph1: 4 (66.7) Phase 2 Expansion Cohort < 70 ULO 800 mg + LDAC - Ph2: 4 (15.4), ULO 1000 mg + LDAC - Ph2: 3 (21.4), LDAC - Ph2: 3 (12.5), Total - Ph2: 10 (15.6) >= 70 ULO 800 mg + LDAC - Ph2: 22 (84.6), ULO 1000 mg + LDAC - Ph2: 11(78.6), LDAC - Ph2: 21 (87.5), Total - Ph2: 54 (84.4) Gender, n (%) Female ULO 600 mg + LDAC - Ph1: 3 (100.0), ULO 800 mg + LDAC - Ph1: 0, Total - Ph1: 3 (50.0) ULO 800 mg + LDAC - Ph2: 9 (34.6), ULO 1000 mg + LDAC - Ph2: 7 (50.0), LDAC - Ph2: 14 (58.3), Total - Ph2: 30 (46.9) Male ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 3 (100.0), Total - Ph1: 3 (50.0) ULO 800 mg + LDAC - Ph2: 17 (65.4), ULO 1000 mg + LDAC - Ph2: 7 (50.0), LDAC - Ph2: 10 (41.7), Total - Ph2: 34 (53.1) Race, n (%) Phase 1 Escalation Cohort Japanese ULO 600 mg + LDAC - Ph1: 3 (100.0), ULO 800 mg + LDAC - Ph1: 3 (100.0), Total - Ph1: 6 (100.0) Phase 2 Expansion Cohort White ULO 800 mg + LDAC - Ph2: 15 (57.7), ULO 1000 mg + LDAC - Ph2: 4 (28.6), LDAC - Ph2: 12 (50.0), Total - Ph2: 31 (48.4) Black/African American ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0, Total - Ph2: 0 Japanese ULO 800 mg + LDAC - Ph2: 6 (23.1), ULO 1000 mg + LDAC - Ph2: 6 (42.9), LDAC - Ph2: 4 (16.7), Total - Ph2: 16 (25.0) Chinese ULO 800 mg + LDAC - Ph2: 2 (7.7), ULO 1000 mg + LDAC - Ph2: 2 (14.3), LDAC - Ph2: 3 (12.5), Total - Ph2: 7 (10.9) Asian Indian ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0, Total - Ph2: 0 Asian Other ULO 800 mg + LDAC - Ph2: 3 (11.5), ULO 1000 mg + LDAC - Ph2: 0 (0.0), LDAC - Ph2: 2 (8.3), Total - Ph2: 5 (7.8) American Indian/Alaska Native ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1 (7.1), LDAC - Ph2: 0, Total - Ph2: 1 (1.6) Native Hawaian/Other Pacific Islander ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0, Total - Ph2: 0 Other ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1 (7.1), LDAC - Ph2: 3 (12.5), Total - Ph2: 4 (6.3) |
| / | 第1相試験Escalationコホートに7例が組み入れられ，6例が投与を受けた。第2相試験Expansionコホートでは，約120例の被験者を投与予定であったが，合計で97例が組み入れられ，64例がランダム化され，62例が投与を受けた。 投与期 開始例数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 24例 完了例数 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例 未完了例数 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 2例 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 24例 未完了の理由，n 病勢進行 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 15例, ULO 1000 mg + LDAC - Ph2群: 6例, LDAC - Ph2群: 6例 治験薬毒性 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 2例 死亡 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 1例 治験薬と関連なしと判定された有害事象 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 2例 被験者からの治験治療の中止申し出 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 2例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 被験者による同意撤回 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 1例 最大臨床効果 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 低コンプライアンス/不遵守 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 依頼者の管理上の理由 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 その他の理由 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 1例 ランダム化された未投与例 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 2例 Ulocuplumab追加投与後に病勢進行 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 4例 Ulocuplumab追加投与後のその他の理由 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 Ulocuplumab追加投与後に中止の申し出 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 追跡期 開始例数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 ULO 800 mg + LDAC - Ph2群: 11例, ULO 1000 mg + LDAC - Ph2群: 6例, LDAC - Ph2群: 12例 完了例数 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例 未完了例数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 ULO 800 mg + LDAC - Ph2群: 11例, ULO 1000 mg + LDAC - Ph2群: 6例, LDAC - Ph2群: 12例 未完了の理由，n 死亡 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 5例, ULO 1000 mg + LDAC - Ph2群: 4例, LDAC - Ph2群: 7例 被験者による同意撤回 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 その他の理由 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 治験実施計画書により追跡不要 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 ULO 800 mg + LDAC - Ph2群: 4例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 4例 |
For the Phase 1 escalation cohort, 7 subjects were enrolled and 6 of those subjects were treated. For the Phase 2 expansion cohort, approximately 120 subjects were planned to be treated. In total, 97 subjects were enrolled, 64 were randomized, and 62 were treated. Treatment Period Started, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 24 Completed, n ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0 Not Completed, n ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 2 ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 24 Reasons for Not Completed, n Disease Progression ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 15, ULO 1000 mg + LDAC - Ph2: 6, LDAC - Ph2: 6 Study Drug Toxicity ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 2 Death ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 1 Adverse Event Unrelated to Drug ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 2 Subject Request to Stop Therapy ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 Subject Withdrew Consent ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 1 Maximum Clinical Benefit ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Poor/Non-Compliance ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Administrative Reason by Sponsor ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Other Reason ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 1 Randomized but Not Treated ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 2 Added ULO, Then Disease Progression ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 4 Added ULO, Then Other Reason ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Added ULO, Then Request to Stop ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Follow-up Period Started, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 ULO 800 mg + LDAC - Ph2: 11, ULO 1000 mg + LDAC - Ph2: 6, LDAC - Ph2: 12 Completed, n ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0 Not Completed, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 ULO 800 mg + LDAC - Ph2: 11, ULO 1000 mg + LDAC - Ph2: 6, LDAC - Ph2: 12 Reasons for Not Completed, n Death ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 5, ULO 1000 mg + LDAC - Ph2: 4, LDAC - Ph2: 7 Subject Withdrew Consent ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 Other Reason ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 Follow-up No Longer Required per Protocol ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 ULO 800 mg + LDAC - Ph2: 4, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 4 |
| / | 第1相試験Escalationコホートの試験期間中に死亡は報告されなかった。第2相試験Expansionコホートにおいて，45例 （72.6%）の死亡が認められ，各治療群における割合は同程度であった（ULO 800 mg + LDAC - Ph2群が73.1%，ULO 1000 mg + LDAC - Ph2群が71.4%，LDAC - Ph2群が72.7%）。最も多く報告された死亡理由は当該疾患（43.5%）であり，治験薬と関連なしと判定された有害事象を含む「その他」（17.7%）が続いた。 第2相試験Expansionコホート 死亡, n (%) ULO 800 mg + LDAC - Ph2群: 19/26例 (73.1), ULO 1000 mg + LDAC - Ph2群: 10/14例 (71.4), LDAC - Ph2群: 16/22例 (72.7), 合計 - Ph2群: 45/62例 (72.6) 死亡理由, n (%) 当該疾患 ULO 800 mg + LDAC - Ph2群: 10/26例 (38.5), ULO 1000 mg + LDAC - Ph2群: 6/14例 (42.9), LDAC - Ph2群: 11/22例 (50.0), 合計 - Ph2群: 27/62例 (43.5) 治験薬毒性 ULO 800 mg + LDAC - Ph2群: 0/26例 (0.0), ULO 1000 mg + LDAC - Ph2群: 1/14例 (7.1), LDAC - Ph2群: 1/22例 (4.5), 合計 - Ph2群: 2/62例 (3.2) 不明 ULO 800 mg + LDAC - Ph2群: 2/26例 (7.7), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.0), LDAC - Ph2群: 3/22例 (13.6), 合計 - Ph2群: 5/62例 (8.1) その他 ULO 800 mg + LDAC - Ph2群: 7/26例 (26.9), ULO 1000 mg + LDAC - Ph2群: 3/14例 (21.4), LDAC - Ph2群: 1/22例 (4.5), 合計 - Ph2群: 11/62例 (17.7) 治験薬最終投与後30 日以内の死亡, n (%) ULO 800 mg + LDAC - Ph2群: 12/26例 (46.2), ULO 1000 mg + LDAC - Ph2群: 5/14例 (35.7), LDAC - Ph2群: 9/22例 (40.9), 合計 - Ph2群: 26/62例 (41.9) 第1相試験Escalationコホートにおいて，重篤な有害事象が3例で報告された（すべての被験者の50%）。すべての重篤な有害事象はGrade 3で治験薬と関連ありと判定された。 第2相試験Expansionコホートにおいて，治験薬の投与を受けたすべての被験者の71.0%で重篤な有害事象が報告され，ULO 800 mg + LDAC - Ph2群では80.8%，ULO 1000 mg + LDAC - Ph2群では57.1%，LDAC - Ph2群では68.2%であった。Grade 3-4及びGrade 5の重篤な有害事象がそれぞれすべての被験者の35.5%及び33.9%で発現した。治験薬と関連ありと判定された重篤な有害事象が16例（25.8%）で認められ，ULO 800 mg + LDAC - Ph2群が8例，ULO 1000 mg + LDAC - Ph2群が2例，LDAC - Ph2群が6例であった。すべての治療群において最も多く認められた治験薬と関連ありと判定された重篤な有害事象は発熱性好中球減少症（14.5%），敗血症（4.8%），腫瘍崩壊症候群（4.8%）であった。 重篤な有害事象（事象名はMedDRA ver. 22.0を用い，事象は体系的評価により収集），n (%) ULO 600 mg + LDAC - Ph1群: 2/3例 (66.67), ULO 800 mg + LDAC - Ph1群: 1/3例 (33.33) ULO 800 mg + LDAC - Ph2群: 21/26例 (80.77), ULO 1000 mg + LDAC - Ph2群: 8/14例 (57.14), LDAC - Ph2群: 15/22例 (68.18) 第1相試験Escalationコホートにおいて，重篤な有害事象が3例で報告された（すべての被験者の50%）。すべての重篤な有害事象はGrade 3で治験薬と関連ありと判定された。 第2相試験Expansionコホートにおいて，治験薬の投与を受けたすべての被験者の71.0%で重篤な有害事象が報告され，ULO 800 mg + LDAC - Ph2群では80.8%，ULO 1000 mg + LDAC - Ph2群では57.1%，LDAC - Ph2群では68.2%であった。Grade 3-4及びGrade 5の重篤な有害事象がそれぞれすべての被験者の35.5%及び33.9%で発現した。治験薬と関連ありと判定された重篤な有害事象が16例（25.8%）で認められ，ULO 800 mg + LDAC - Ph2群が8例，ULO 1000 mg + LDAC - Ph2群が2例，LDAC - Ph2群が6例であった。すべての治療群において最も多く認められた治験薬と関連ありと判定された重篤な有害事象は発熱性好中球減少症（14.5%），敗血症（4.8%），腫瘍崩壊症候群（4.8%）であった。 重篤な有害事象（事象名はMedDRA ver. 22.0を用い，事象は体系的評価により収集），n (%) ULO 600 mg + LDAC - Ph1群: 2/3例 (66.67), ULO 800 mg + LDAC - Ph1群: 1/3例 (33.33) ULO 800 mg + LDAC - Ph2群: 21/26例 (80.77), ULO 1000 mg + LDAC - Ph2群: 8/14例 (57.14), LDAC - Ph2群: 15/22例 (68.18) 2例以上で認められた重篤な有害事象 血液およびリンパ系障害 発熱性好中球減少症 ULO 600 mg + LDAC - Ph1群: 2/3例 (66.67), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 8/26例 (30.77), ULO 1000 mg + LDAC - Ph2群: 5/14例 (35.71), LDAC - Ph2群: 6/22例 (27.27) 胃腸障害 下痢 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 2/26例 (7.69), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 2/22例 (9.09) 胃腸出血 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 2/26例 (7.69), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 0/22例 (0.00) 感染症および寄生虫症 肺感染 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 2/26例 (7.69), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 0/22例 (0.00) 肺炎 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 3/26例 (11.54), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 1/22例 (4.55) 敗血症 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 3/26例 (11.54), ULO 1000 mg + LDAC - Ph2群: 2/14例 (14.29), LDAC - Ph2群: 1/22例 (4.55) 敗血症性ショック ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 1/26例 (3.85), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 1/22例 (4.55) 代謝および栄養障害 脱水 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 1/26例 (3.85), ULO 1000 mg + LDAC - Ph2群: 0/14例 (0.00), LDAC - Ph2群: 1/22例 (4.55) 腫瘍崩壊症候群 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 1/26例 (3.85), ULO 1000 mg + LDAC - Ph2群: 1/14例 (7.14), LDAC - Ph2群: 1/22例 (4.55) 良性、悪性および詳細不明の新生物（嚢胞およびポリープを含む） 悪性新生物進行 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 5/26例 (19.23), ULO 1000 mg + LDAC - Ph2群: 2/14例 (14.29), LDAC - Ph2群: 6/22例 (27.27) 呼吸器、胸郭および縦隔障害 肺水腫 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 1/26例 (3.85), ULO 1000 mg + LDAC - Ph2群: 1/14例 (7.14), LDAC - Ph2群: 1/22例 (4.55) 呼吸不全 ULO 600 mg + LDAC - Ph1群: 0/3例 (0.00), ULO 800 mg + LDAC - Ph1群: 0/3例 (0.00) ULO 800 mg + LDAC - Ph2群: 2/26例 (7.69), ULO 1000 mg + LDAC - Ph2群: 1/14例 (7.14), LDAC - Ph2群: 0/22例 (0.00) 第1相試験Escalationコホートにおいて中止に至った有害事象は認められなかった。 第2相試験Expansionコホートにおいて，中止に至った有害事象が認められた被験者は14例（22.6%）であり，このうち7例はULO 800 mg + LDAC - Ph2群，3例はULO 1000 mg + LDAC - Ph2群，4例はLDAC - Ph2群で認められた。中止に至った有害事象のうち2件は治験薬と関連ありと判定され，これらはULO 800 mg + LDAC - Ph2群の被験者で認められたGrade 4の発熱性好中球減少症及びULO 1000 mg + LDAC - Ph2群の被験者で認められたGrade 2の間質性肺疾患であった。 第1相試験Escalationコホートの6例すべての被験者に1件以上の有害事象が認められた。すべての被験者において1件以上の血液およびリンパ系障害の有害事象が認められた（貧血，発熱性好中球減少症，播種性血管内凝固を含む）。また，すべての被験者において1件以上の治験薬と関連ありと判定された有害事象が認めれた。 第2相試験Expansionコホートでは，ほとんどの被験者（98.4%）において重症度に関わらず1件以上の有害事象が認められた。Grade 3-4及びGrade 5の有害事象がそれぞれ53.2%及び33.9%の被験者において発現した。 最も多く認められた有害事象の分類は胃腸障害（重症度に関わらず，悪心32.3%，便秘27.4%，下痢27.4%），血液およびリンパ系障害（重症度に関わらず，発熱性好中球減少症48.4%，貧血35.5%，血小板減少症12.9%）及び一般・全身障害および投与部位の状態（重症度に関わらず，発熱30.6%，疲労22.6%，末梢性浮腫17.7%）であった。44例（71%）の被験者において治験薬と関連ありと判定された有害事象が認められた。治験薬と関連ありと判定されたGrade 3-4の有害事象が被験者の51.6%で発現した。治験薬と関連ありと判定されたGrade 5の敗血症がULO 1000 mg + LDAC - Ph2群の1例で認められた。3つの最も多く認められた治験薬と関連ありと判定された有害事象の分類は血液およびリンパ系障害（貧血29%，発熱性好中球減少症29%），胃腸障害（悪心22.6%）及び臨床検査（血小板数減少25.8%，好中球数減少12.9%）であった。 |
There were no deaths reported during study participation in the Phase 1 escalation cohort. There were 45 deaths (72.6%) in the Phase 2 expansion cohort, which was balanced between treatment groups (73.1% of subjects treated with ulocuplumab 800 mg + LDAC, 71.4% of subjects treated with ulocuplumab 1000 mg + LDAC, and 72.7% of subjects treated with LDAC only). The most commonly reported cause of death was disease (43.5%), followed by 'Other' (17.7%), which included adverse events unrelated to study drug. Phase 2 Expansion Cohort Death, Affected/at Risk (%) ULO 800 mg + LDAC - Ph2: 19/26 (73.1), ULO 1000 mg + LDAC - Ph2: 10/14 (71.4), LDAC - Ph2: 16/22 (72.7), Total - Ph2: 45/62 (72.6) Cause of Death, Affected/at Risk (%) Disease ULO 800 mg + LDAC - Ph2: 10/26 (38.5), ULO 1000 mg + LDAC - Ph2: 6/14 (42.9), LDAC - Ph2: 11/22 (50.0), Total - Ph2: 27/62 (43.5) Study Drug Toxicity ULO 800 mg + LDAC - Ph2: 0/26 (0.0), ULO 1000 mg + LDAC - Ph2: 1/14 (7.1), LDAC - Ph2: 1/22 (4.5), Total - Ph2: 2/62 (3.2) Unknown ULO 800 mg + LDAC - Ph2: 2/26 (7.7), ULO 1000 mg + LDAC - Ph2: 0/14 (0.0), LDAC - Ph2: 3/22 (13.6), Total - Ph2: 5/62 (8.1) Other ULO 800 mg + LDAC - Ph2: 7/26 (26.9), ULO 1000 mg + LDAC - Ph2: 3/14 (21.4), LDAC - Ph2: 1/22 (4.5), Total - Ph2: 11/62 (17.7) Death within 30 Days of Last Dose of Study Medication, Affected/at Risk (%) ULO 800 mg + LDAC - Ph2: 12/26 (46.2), ULO 1000 mg + LDAC - Ph2: 5/14 (35.7), LDAC - Ph2: 9/22 (40.9), Total - Ph2: 26/62 (41.9) In the Phase 1 escalation cohort, serious adverse events were reported in 3 subjects (50% of all subjects). All serious adverse events were Grade 3 and considered related to study drug. In the Phase 2 expansion cohort, serious adverse events were reported in 71.0% of all-treated subjects, including 80.8% of subjects treated with ulocuplumab 800 mg + LDAC, 57.1% of subjects treated with ulocuplumab 1000 mg + LDAC, and 68.2% of subjects treated with LDAC. Grade 3-4 and Grade 5 serious adverse events occurred in 35.5% and 33.9% of all subjects, respectively. Sixteen subjects (25.8%) experienced an serious adverse event that was considered related to study drug; 8 subjects in the ulocuplumab + 800 mg group, 2 in the ulocuplumab + 1000 mg group, and 6 in the LDAC group. The most common serious adverse events related to study drugs across all groups were febrile neutropenia (14.5%), sepsis (4.8%), and tumor lysis syndrome (4.8%). Serious Adverse Events (Term from MedDRA ver. 22.0, Events were collected by systematic assessment), Affected/at Risk (%) ULO 600 mg + LDAC - Ph1: 2/3 (66.67), ULO 800 mg + LDAC - Ph1: 1/3 (33.33) ULO 800 mg + LDAC - Ph2: 21/26 (80.77), ULO 1000 mg + LDAC - Ph2: 8/14 (57.14), LDAC - Ph2: 15/22 (68.18) Serious Adverse Events in >= 2 Subjects Blood and Lymphatic System Disorders Febrile neutropenia ULO 600 mg + LDAC - Ph1: 2/3 (66.67), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 8/26 (30.77), ULO 1000 mg + LDAC - Ph2: 5/14 (35.71), LDAC - Ph2: 6/22 (27.27) Gastrointestinal disorders Diarrhoea ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 2/26 (7.69), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 2/22 (9.09) Gastrointestinal haemorrhage ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 2/26 (7.69), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 0/22 (0.00) Infections and Infestations Lung infection ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 2/26 (7.69), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 0/22 (0.00) Pneumonia ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 3/26 (11.54), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 1/22 (4.55) Sepsis ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 3/26 (11.54), ULO 1000 mg + LDAC - Ph2: 2/14 (14.29), LDAC - Ph2: 1/22 (4.55) Septic shock ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 1/26 (3.85), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 1/22 (4.55) Metabolism and nutrition disorders Dehydration ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 1/26 (3.85), ULO 1000 mg + LDAC - Ph2: 0/14 (0.00), LDAC - Ph2: 1/22 (4.55) Tumor lysis syndrome ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 1/26 (3.85), ULO 1000 mg + LDAC - Ph2: 1/14 (7.14), LDAC - Ph2: 1/22 (4.55) Neoplasms Benign, Malignant and Unspecified (incl Cysts and Polyps) Malignant neoplasm progression ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 5/26 (19.23), ULO 1000 mg + LDAC - Ph2: 2/14 (14.29), LDAC - Ph2: 6/22 (27.27) Respiratory, thoracic and mediastinal disorders Pulmonary oedema ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 1/26 (3.85), ULO 1000 mg + LDAC - Ph2: 1/14 (7.14), LDAC - Ph2: 1/22 (4.55) Respiratory failure ULO 600 mg + LDAC - Ph1: 0/3 (0.00), ULO 800 mg + LDAC - Ph1: 0/3 (0.00) ULO 800 mg + LDAC - Ph2: 2/26 (7.69), ULO 1000 mg + LDAC - Ph2: 1/14 (7.14), LDAC - Ph2: 0/22 (0.00) There were no adverse events leading to discontinuation in the Phase 1 escalation cohort. In the Phase 2 expansion cohort, there were 14 subjects (22.6%) who had an adverse event that led to discontinuation. Seven of these subjects received ulocuplumab 800 mg + LDAC, 3 received ulocuplumab 1000 mg + LDAC, and 4 received LDAC alone. Two of all adverse events leading to discontinuation were considered related to study drug. These were due to Grade 4 febrile neutropenia in a subject receiving ulocuplumab 800 mg + LDAC, and Grade 2 interstitial lung disease in a subject receiving ulocuplumab 1000 mg + LDAC. All 6 subjects experienced at least one adverse event in the Phase 1 escalation cohort. All subjects experienced at least one blood and lymphatic system disorder (including anemia, febrile neutropenia, or disseminated intravascular coagulation). All subjects also experienced at least one adverse event related to study drug. In the Phase 2 expansion cohort, a majority of subjects (98.4%) experienced at least one adverse event of any grade. Grade 3-4, and Grade 5 adverse events occurred in 53.2% and 33.9% of all subjects, respectively. The three most common categories of adverse events were gastrointestinal disorders (any grade nausea 32.3%, constipation 27.4%, and diarrhea 27.4%), blood and lymphatic system disorders (any grade febrile neutropenia 48.4%, anemia 35.5%, and thrombocytopenia 12.9%), and general disorders and administration site conditions (any grade pyrexia 30.6%, fatigue 22.6%, and edema peripheral 17.7%). Forty-four subjects (71%) experienced an adverse event related to study drug. Grade 3-4 adverse events related to study drug occurred in 51.6% of all subjects. One subject experienced a Grade 5 adverse event of sepsis related to study drug. This subject was in the ulocuplumab 1000 mg + LDAC group. The three most common categories of adverse events related to study drug were blood and lymphatic system disorders (anemia 29% and febrile neutropenia 29%), gastrointestinal disorders (nausea 22.6%), and investigations (platelet count decreased 25.8% and neutrophil count decreased 12.9%). |
| / | 第1相試験Escalationコホート 評価対象被験者数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 主要評価項目： 1コース目に用量制限毒性が認められた被験者数 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 有害事象が認められた被験者数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 Grade 3以上の有害事象が認められた被験者数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 中止に至った有害事象が認められた被験者数 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 重篤な有害事象が認められた被験者数 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 死亡症例数 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 臨床検査値異常が認められた被験者数 絶対好中球数 - grade 3 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 絶対好中球数 - grade 4 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 アラニンアミノトランスフェラーゼ (ALT) - grade 0 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 2例 ALT - grade 1 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 アルブミン - grade 0 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 0例 アルブミン - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 2例 アルブミン - grade 2 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 アルカリホスファターゼ (ALP) - grade 0 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 2例 ALP grade 1 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 アスパラギン酸アミノトランスフェラーゼ (AST) - grade 0 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 AST - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 総ビリルビン - grade 0 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 総ビリルビン - grade 2 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 総カルシウム - grade 0 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 総カルシウム - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 総カルシウム - grade 2 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 クレアチンキナーゼ - grade 0 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 クレアチニン - grade 0 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 3例 クレアチニン - grade 1 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1: 0例 フィブリノーゲン - grade 0 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 0例 空腹時血清血糖 - grade 0 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 空腹時血清血糖 - grade 1 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 0例 空腹時血清血糖 - grade 2 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 2例 ヘモグロビン - grade 2 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 ヘモグロビン - grade 3 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 2例 白血球 - grade 0 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 白血球 - grade 3 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 1例 白血球 - grade 4 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 総リパーゼ（比色分析）- grade 0 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 総リパーゼ（比色分析）- grade 1 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 0例 総リパーゼ（比色分析）- grade 3 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 2例 リンパ球（絶対値）- grade 0 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 リンパ球（絶対値）- grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 リンパ球（絶対値）- grade 2 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 リンパ球（絶対値）- grade 3 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 0例 好中球（絶対値）- grade 3 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 好中球（絶対値）- grade 4 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 無機リン - grade 0 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 無機リン - grade 3 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 血小板数 - grade 3 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 血小板数 - grade 4 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 血清カリウム - grade 0 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 2例 血清カリウム - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 血清カリウム - grade 3 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 0例 血清ナトリウム - grade 0 ULO 600 mg + LDAC - Ph1群: 2例, ULO 800 mg + LDAC - Ph1群: 1例 血清ナトリウム - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 2例 血清ナトリウム - grade 3 ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 0例 尿酸 - grade 0 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 2例 尿酸 - grade 1 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 1例 第2相試験Expansionコホート ULO 800 mg + LDAC - Ph2群の26例中4例，ULO 1000 mg + LDAC - Ph2群の14例中1例及びLDAC - Ph2群の24例中6例が完全寛解/血球数が未回復な完全寛解（CR/CRi）を達成した。これは各群それぞれ15.4%，7.1%及び25.0%の完全寛解率に相当する。 評価対象被験者数 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 24例 主要評価項目：最良総合効果, % (95% CI) ULO 800 mg + LDAC - Ph2群: 15.4 (4.4-34.9), ULO 1000 mg + LDAC - Ph2群: 7.1 (0.2-33.9), LDAC - Ph2群: 25.0 (9.8-46.7) |
Phase 1 Escalation Cohort Overall Number of Subjects Analyzed, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 Primary Outcome: Number of Subjects with Dose-Limiting Toxicities (DLTs) in Treatment Cycle 1, n ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 Number of Subjects With adverse events, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 Number of Subjects With >= Grade 3 adverse events, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 Number of Subjects With adverse events Leading to Discontinuation, n ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 Number of Subjects With serious adverse events, n ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 Number of Deaths, n ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 Number of Subjects With Laboratory Abnormalities, n ABSOLUTE NEUTROPHIL COUNT - grade 3 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 ABSOLUTE NEUTROPHIL COUNT - grade 4 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 ALANINE AMINOTRANSFERASE (ALT) - grade 0 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 2 ALT - grade 1 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 ALBUMIN - grade 0 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 ALBUMIN - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 2 ALBUMIN - grade 2 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 ALKALINE PHOSPHATASE (ALP) - grade 0 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 2 ALP grade 1 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 ASPARTATE AMINOTRANSFERASE (AST) - grade 0 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 AST - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 BILIRUBIN, TOTAL - grade 0 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 BILIRUBIN, TOTAL - grade 2 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 CALCIUM, TOTAL - grade 0 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 CALCIUM, TOTAL - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 CALCIUM, TOTAL - grade 2 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 CREATINE KINASE - grade 0 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 CREATININE - grade 0 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 3 CREATININE - grade 1 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 FIBRINOGEN - grade 0 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 GLUCOSE, FASTING SERUM - grade 0 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 GLUCOSE, FASTING SERUM - grade 1 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 0 GLUCOSE, FASTING SERUM - grade 2 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 2 HEMOGLOBIN - grade 2 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 HEMOGLOBIN - grade 3 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 2 LEUKOCYTES - grade 0 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 LEUKOCYTES - grade 3 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 1 LEUKOCYTES - grade 4 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 0 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 1 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 LIPASE, TOTAL (COLORIMETRIC ASSAY) - grade 3 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 2 LYMPHOCYTES (ABSOLUTE) - grade 0 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 LYMPHOCYTES (ABSOLUTE) - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 LYMPHOCYTES (ABSOLUTE) - grade 2 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 LYMPHOCYTES (ABSOLUTE) - grade 3 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 NEUTROPHILS (ABSOLUTE) - grade 3 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 NEUTROPHILS (ABSOLUTE) - grade 4 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 PHOSPHORUS, INORGANIC - grade 0 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 PHOSPHORUS, INORGANIC - grade 3 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 PLATELET COUNT - grade 3 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 PLATELET COUNT - grade 4 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 POTASSIUM, SERUM - grade 0 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 2 POTASSIUM, SERUM - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 POTASSIUM, SERUM - grade 3 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 0 SODIUM, SERUM - grade 0 ULO 600 mg + LDAC - Ph1: 2, ULO 800 mg + LDAC - Ph1: 1 SODIUM, SERUM - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 2 SODIUM, SERUM - grade 3 ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 0 URIC ACID - grade 0 ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 2 URIC ACID - grade 1 ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 1 Phase 2 Expansion Cohort Four of 26 subjects achieved complete response/complete response with incomplete blood count (CR/CRi) in the ulocuplumab 800 mg + LDAC group, 1 of 14 subjects achieved CR/CRi in the ulocuplumab 1000 mg + LDAC group, and 6 of 24 subjects achieved CR/CRi in the LDAC alone group. This corresponds to complete remission rates of 15.4%, 7.1%, and 25.0% in each group, respectively. Overall Number of Subjects Analyzed, n ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 24 Primary Outcome: Best Overall Response (BOR), % (95% CI) ULO 800 mg + LDAC - Ph2: 15.4 (4.4 to 34.9), ULO 1000 mg + LDAC - Ph2: 7.1 (0.2 to 33.9), LDAC - Ph2: 25.0 (9.8 to 46.7) |
| 副次的評価項目の解析結果 / Secondary Outcome Measures | 第1相試験Escalationコホート 副次評価項目：最良総合効果 治験責任医師の評価による全体的な完全寛解（CR/CRi）が6例中4例（66%）で認められた。ULO 600 mg + LDAC - Ph1群の1例及びULO 800 mg + LDAC - Ph1群の3例すべてにおいて最良総合効果が完全寛解であった。 評価対象被験者数 ULO 600 mg + LDAC - Ph1群: 3例, ULO 800 mg + LDAC - Ph1群: 3例 副次評価項目：最良総合効果, n ULO 600 mg + LDAC - Ph1群: 1例, ULO 800 mg + LDAC - Ph1群: 3例 第2相試験Expansionコホート 評価対象被験者数 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 22例 副次評価項目： 有害事象が認められた被験者数 ULO 800 mg + LDAC - Ph2群: 25例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC - Ph2群: 22例 中止に至った有害事象が認められた被験者数 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 4例 重篤な有害事象が認められた被験者数 ULO 800 mg + LDAC - Ph2群: 21例, ULO 1000 mg + LDAC - Ph2群: 8例, LDAC - Ph2群: 15例 死亡症例数 ULO 800 mg + LDAC - Ph2群: 19例, ULO 1000 mg + LDAC - Ph2群: 10例, LDAC - Ph2群: 16例 臨床検査値異常が認められた被験者数 ALT, grade 1 ULO 800 mg + LDAC - Ph2群: 5例, ULO 1000 mg + LDAC - Ph2群: 5例, LDAC - Ph2群: 4例 ALT, grade 2 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 2例 ALT, grade 3 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 0例 ALP, grade 1 ULO 800 mg + LDAC - Ph2群: 9例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 8例 ALP, grade 2 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 5例, LDAC - Ph2群: 2例 AST, grade 1 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 8例, LDAC - Ph2群: 4例 AST, grade 2 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 2例 AST, grade 3 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 総ビリルビン, grade 1 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 1例 総ビリルビン, grade 2 ULO 800 mg + LDAC - Ph2群: 4例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 1例 総ビリルビン, grade 3 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例 クレアチニン, grade 1 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 5例, LDAC - Ph2群: 6例 クレアチニン, grade 2 ULO 800 mg + LDAC - Ph2群: 5例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 2例 総カルシウム, grade 1 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 3例 総カルシウム, grade 2 ULO 800 mg + LDAC - Ph2群: 5例, ULO 1000 mg + LDAC - Ph2群: 5例, LDAC - Ph2群: 7例 総カルシウム, grade 3 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 無機リン, grade 1 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 無機リン, grade 2 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 1例 無機リン, grade 3 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 2例 無機リン, grade 4 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 血清カリウム, grade 1 ULO 800 mg + LDAC - Ph2群: 4例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 5例 血清カリウム, grade 2 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 血清カリウム, grade 3 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 4例 血清カリウム, grade 4 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 血清ナトリウム, grade 1 ULO 800 mg + LDAC - Ph2群: 9例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 7例 血清ナトリウム, grade 2 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 血清ナトリウム, grade 3 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 3例, LDAC - Ph2群: 4例 ヘモグロビン, grade 2 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 4例, LDAC - Ph2群: 4例 ヘモグロビン, grade 3 ULO 800 mg + LDAC - Ph2群: 22例, ULO 1000 mg + LDAC - Ph2群: 10例, LDAC - Ph2群: 17例 血小板数, grade 2 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 血小板数, grade 3 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 3例 血小板数, grade 4 ULO 800 mg + LDAC - Ph2群: 23例, ULO 1000 mg + LDAC - Ph2群: 13例, LDAC - Ph2群: 17例 絶対好中球数, grade 1 ULO 800 mg + LDAC - Ph2群: 2例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 0例 絶対好中球数, grade 2 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 1例 絶対好中球数, grade 3 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 絶対好中球数, grade 4 ULO 800 mg + LDAC - Ph2群: 18例, ULO 1000 mg + LDAC - Ph2群: 10例, LDAC - Ph2群: 16例 白血球, grade 1 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 白血球, grade 2 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 4例, LDAC - Ph2群: 0例 白血球, grade 3 ULO 800 mg + LDAC - Ph2群: 6例, ULO 1000 mg + LDAC - Ph2群: 4例, LDAC - Ph2群: 5例 白血球, grade 4 ULO 800 mg + LDAC - Ph2群: 8例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 10例 リンパ球（絶対値）, grade 1 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 4例, LDAC - Ph2群: 1例 リンパ球（絶対値）, grade 2 ULO 800 mg + LDAC - Ph2群: 7例, ULO 1000 mg + LDAC - Ph2群: 1例, LDAC - Ph2群: 7例 リンパ球（絶対値）, grade 3 ULO 800 mg + LDAC - Ph2群: 5例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 7例 リンパ球（絶対値）, grade 4 ULO 800 mg + LDAC - Ph2群: 0例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 好中球（絶対値）, grade 1 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 0例 好中球（絶対値）, grade 2 ULO 800 mg + LDAC - Ph2群: 1例, ULO 1000 mg + LDAC - Ph2群: 2例, LDAC - Ph2群: 1例 好中球（絶対値）, grade 3 ULO 800 mg + LDAC - Ph2群: 3例, ULO 1000 mg + LDAC - Ph2群: 0例, LDAC - Ph2群: 1例 好中球（絶対値）, grade 4 ULO 800 mg + LDAC - Ph2群: 18例, ULO 1000 mg + LDAC - Ph2群: 10例, LDAC - Ph2群: 16例 評価対象被験者数 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例 副次評価項目：低用量シタラビンと併用でのulocuplumabを2つの異なる用量（800 mg及び1000 mg）で投与したときの全寛解率, % (95%CI) ULO 800 mg + LDAC - Ph2群: 19.2 (6.6-39.4), ULO 1000 mg + LDAC - Ph2群: 7.1 (0.2-33.9) 評価対象被験者数 ULO 800 mg + LDAC - Ph2群: 4例, ULO 1000 mg + LDAC - Ph2群: 1例 副次評価項目：低用量シタラビンと併用でのulocuplumabを2つの異なる用量（800 mg及び1000 mg）で投与したときのCR/CRiを達成した被験者における奏効期間, 中央値（範囲） ULO 800 mg + LDAC - Ph2群: 2.4ヵ月 (0.5-5.6), ULO 1000 mg + LDAC - Ph2群: 4.3ヵ月 (NA-NA) 評価対象被験者数 LDAC - Ph2群: 24例 副次評価項目：低用量シタラビンを単剤投与したときの完全寛解（CR/CRi）率及び全寛解率, % (95%CI) CR/CRi率：LDAC - Ph2群: 25.0 (9.8-46.7)，全寛解率：LDAC - Ph2群：25.0 (9.8-46.7) 評価対象被験者数 LDAC - Ph2群: 6例 副次評価項目：低用量シタラビンを単剤投与したときのCR/CRiを達成した被験者における奏効期間, 中央値（範囲） LDAC - Ph2群: 5.7ヵ月 (0.9-NA) 第1相試験Escalationコホート及び第2相試験Expansionコホート 第1相試験Escalationコホートでは，全生存期間データは収集されなかった。 第2相試験Expansionコホートにおいて，全生存期間の中央値はULO 800 mg + LDAC - Ph2群で3.3ヵ月，ULO 1000 mg + LDAC - Ph2群で3.0ヵ月，LDAC - Ph2群で6.9ヵ月であった。 評価対象被験者数 ULO 600 mg + LDAC - Ph1群: 0例, ULO 800 mg + LDAC - Ph1群: 0例 ULO 800 mg + LDAC - Ph2群: 26例, ULO 1000 mg + LDAC - Ph2群: 14例, LDAC -Ph2群: 22例 副次評価項目：全生存期間，中央値（範囲） ULO 600 mg + LDAC - Ph1群: NA, ULO 800 mg + LDAC - Ph1群: NA ULO 800 mg + LDAC - Ph2群: 3.3ヵ月 (1.8-8.7), ULO 1000 mg + LDAC - Ph2群: 3.0ヵ月 (1.8-4.7), LDAC - Ph2群: 6.9ヵ月 (1.6-12.7) | Phase 1 Escalation Cohort Secondary Outcome: BOR Overall complete remission (CR/CRi), as assessed by the investigator, was observed in 4 of 6 evaluable subjects (66%); 1 subject treated with 600 mg ulocuplumab + LDAC had a BOR of CR and all 3 subjects treated with 800 mg ulocuplumab + LDAC had a BOR of CR. Overall Number of Subjects Analyzed, n ULO 600 mg + LDAC - Ph1: 3, ULO 800 mg + LDAC - Ph1: 3 Secondary Outcome: BOR, n ULO 600 mg + LDAC - Ph1: 1, ULO 800 mg + LDAC - Ph1: 3 Phase 2 Expansion Cohort Overall Number of Subjects Analyzed, n ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 22 Secondary Outcome: Number of Subjects With adverse events, n ULO 800 mg + LDAC - Ph2: 25, ULO 1000 mg + LDAC - Ph2: 14, LDAC - Ph2: 22 Number of Subjects With adverse events Leading to Discontinuation, n ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 4 Number of Subjects With serious adverse events, n ULO 800 mg + LDAC - Ph2: 21, ULO 1000 mg + LDAC - Ph2: 8, LDAC - Ph2: 15 Number of Deaths, n ULO 800 mg + LDAC - Ph2: 19, ULO 1000 mg + LDAC - Ph2: 10, LDAC - Ph2: 16 Number of Subjects With Laboratory Abnormalities, n ALT, grade 1 ULO 800 mg + LDAC - Ph2: 5, ULO 1000 mg + LDAC - Ph2: 5, LDAC - Ph2: 4 ALT, grade 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 2 ALT, grade 3 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 0 ALP, grade 1 ULO 800 mg + LDAC - Ph2: 9, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 8 ALP, grade 2 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 5, LDAC - Ph2: 2 AST, grade 1 ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 8, LDAC - Ph2: 4 AST, grade 2 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 2 AST, grade 3 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 BILIRUBIN, TOTAL, grade 1 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 1 BILIRUBIN, TOTAL, grade 2 ULO 800 mg + LDAC - Ph2: 4, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 1 BILIRUBIN, TOTAL, grade 3 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0 CREATININE, grade 1 ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 5, LDAC - Ph2: 6 CREATININE, grade 2 ULO 800 mg + LDAC - Ph2: 5, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 2 CALCIUM, TOTAL, grade 1 ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 3 CALCIUM, TOTAL, grade 2 ULO 800 mg + LDAC - Ph2: 5, ULO 1000 mg + LDAC - Ph2: 5, LDAC - Ph2: 7 CALCIUM, TOTAL, grade 3 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 PHOSPHORUS, INORGANIC, grade 1 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 PHOSPHORUS, INORGANIC, grade 2 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 1 PHOSPHORUS, INORGANIC, grade 3 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 2 PHOSPHORUS, INORGANIC, grade 4 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 POTASSIUM, SERUM, grade 1 ULO 800 mg + LDAC - Ph2: 4, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 5 POTASSIUM, SERUM, grade 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 POTASSIUM, SERUM, grade 3 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 4 POTASSIUM, SERUM, grade 4 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 SODIUM, SERUM, grade 1 ULO 800 mg + LDAC - Ph2: 9, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 7 SODIUM, SERUM, grade 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 SODIUM, SERUM, grade 3 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 3, LDAC - Ph2: 4 HEMOGLOBIN, grade 2 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 4, LDAC - Ph2: 4 HEMOGLOBIN, grade 3 ULO 800 mg + LDAC - Ph2: 22, ULO 1000 mg + LDAC - Ph2: 10, LDAC - Ph2: 17 PLATELET COUNT, grade 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 PLATELET COUNT, grade 3 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 3 PLATELET COUNT, grade 4 ULO 800 mg + LDAC - Ph2: 23, ULO 1000 mg + LDAC - Ph2: 13, LDAC - Ph2: 17 ABSOLUTE NEUTROPHIL COUNT, grade 1 ULO 800 mg + LDAC - Ph2: 2, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 0 ABSOLUTE NEUTROPHIL COUNT, grade 2 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 1 ABSOLUTE NEUTROPHIL COUNT, grade 3 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 ABSOLUTE NEUTROPHIL COUNT, grade 4 ULO 800 mg + LDAC - Ph2: 18, ULO 1000 mg + LDAC - Ph2: 10, LDAC - Ph2: 16 LEUKOCYTES, grade 1 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 LEUKOCYTES, grade 2 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 4, LDAC - Ph2: 0 LEUKOCYTES, grade 3 ULO 800 mg + LDAC - Ph2: 6, ULO 1000 mg + LDAC - Ph2: 4, LDAC - Ph2: 5 LEUKOCYTES, grade 4 ULO 800 mg + LDAC - Ph2: 8, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 10 LYMPHOCYTES (ABSOLUTE), grade 1 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 4, LDAC - Ph2: 1 LYMPHOCYTES (ABSOLUTE), grade 2 ULO 800 mg + LDAC - Ph2: 7, ULO 1000 mg + LDAC - Ph2: 1, LDAC - Ph2: 7 LYMPHOCYTES (ABSOLUTE), grade 3 ULO 800 mg + LDAC - Ph2: 5, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 7 LYMPHOCYTES (ABSOLUTE), grade 4 ULO 800 mg + LDAC - Ph2: 0, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 NEUTROPHILS (ABSOLUTE), grade 1 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 0 NEUTROPHILS (ABSOLUTE), grade 2 ULO 800 mg + LDAC - Ph2: 1, ULO 1000 mg + LDAC - Ph2: 2, LDAC - Ph2: 1 NEUTROPHILS (ABSOLUTE), grade 3 ULO 800 mg + LDAC - Ph2: 3, ULO 1000 mg + LDAC - Ph2: 0, LDAC - Ph2: 1 NEUTROPHILS (ABSOLUTE), grade 4 ULO 800 mg + LDAC - Ph2: 18, ULO 1000 mg + LDAC - Ph2: 10, LDAC - Ph2: 16 Overall Number of Subjects Analyzed, n ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14 Secondary Outcome: Overall Rate of Remission in Subjects Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC, % (95%CI) ULO 800 mg + LDAC - Ph2: 19.2 (6.6 to 39.4), ULO 1000 mg + LDAC - Ph2: 7.1 (0.2 to 33.9) Overall Number of Subjects Analyzed, n ULO 800 mg + LDAC - Ph2: 4, ULO 1000 mg + LDAC - Ph2: 1 Secondary Outcome: Duration of Response in Subjects With CR/CRi Treated With Ulocuplumab at Two Different Dose Levels 800 mg and 1000 mg in Combination With LDAC (month), Median (Range) ULO 800 mg + LDAC - Ph2: 2.4 (0.5 to 5.6), ULO 1000 mg + LDAC - Ph2: 4.3 (NA to NA) Overall Number of Subjects Analyzed, n LDAC - Ph2: 24 Secondary Outcome: Rate of Complete Remission (CR/CRi) and Overall Rate of Remission in Subjects Treated With LDAC Only, % (95%CI) CR/CRi: LDAC - Ph2: 25.0 (9.8 to 46.7), Overall Remission Rate: LDAC - Ph2: 25.0 (9.8 to 46.7) Overall Number of Subjects Analyzed, n LDAC - Ph2: 6 Secondary Outcome: Duration of Response in Subjects With CR/CRi Treated With LDAC Only (month), Median (Range) LDAC - Ph2: 5.7 (0.9 to NA) Phase 1 Escalation Cohort and Phase 2 Expansion Cohort The overall survival data was not collected for the Phase 1 escalation cohort. For the Phase 2 expansion cohort, the median overall survival was 3.3 months in the ulocuplumab 800 mg + LDAC group, 3.0 months in the ulocuplumab 1000 mg + LDAC group, and 6.9 months in the LDAC alone group. Overall Number of Subjects Analyzed, n ULO 600 mg + LDAC - Ph1: 0, ULO 800 mg + LDAC - Ph1: 0 ULO 800 mg + LDAC - Ph2: 26, ULO 1000 mg + LDAC - Ph2: 14, LDAC -Ph2: 22 Secondary Outcome: Overall Survival (month), Median (Range) ULO 600 mg + LDAC - Ph1: NA, ULO 800 mg + LDAC - Ph1: NA ULO 800 mg + LDAC - Ph2: 3.3 (1.8 to 8.7), ULO 1000 mg + LDAC - Ph2: 3.0 (1.8 to 4.7), LDAC - Ph2: 6.9 (1.6 to 12.7) |
| / | 第1相試験コホートでは，急性骨髄性白血病患者におけるulocuplumabと低用量シタラビンの併用療法の安全性及び耐容性が示されたことにより，主要評価項目を達成した。第1相試験コホートは主要な有効性の副次評価項目も達成した（CR/CRiが66%）。 第2相試験コホートでは，主要評価項目及び主要な有効性の副次評価項目を達成しなかった（ULO 800 mg + LDAC - Ph2群，ULO 1000 mg + LDAC - Ph2群及びLDAC - Ph2群のCR/Criがそれぞれ15.4%，7.1%及び25.0%）。 Ulocuplumabの新たな安全性上の懸念は認められなかった。 |
The Phase 1 cohort met the primary endpoint by demonstrating a safe and tolerable profile of the combination of ulocuplumab with LDAC in acute myeloid leukemia subjects. The Phase 1 cohort also met the key secondary efficacy endpoint (CR/CRi of 66%).The Phase 2 cohort did not meet the primary nor key secondary efficacy endpoints (CR/CRi of 15.4%, 7.1% and 25.0% for ulocuplumab 800 mg + LDAC, ulocuplumab 1000 mg + LDAC and LDAC alone, respectively). No new safety concerns were identified for ulocuplumab. |
| 出版物の掲載 / Posting of journal publication | ||
３ IPDシェアリング
３ IPDシェアリング
| / | 無 | No |
|---|---|---|
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管理的事項
管理的事項
| 試験等の種別 | 企業治験 |
|---|---|
| 主たる治験と拡大治験のいずれにも該当しない | |
| 登録日 | 2024年02月22日 |
| jRCT番号 | jRCT2080222750 |
１ 試験等の実施体制に関する事項及び試験等を行う施設の構造設備に関する事項
１ 試験等の実施体制に関する事項及び試験等を行う施設の構造設備に関する事項
（１）試験等の名称
（１）試験等の名称
| 新たに急性骨髄性白血病と診断された患者を対象としたulocuplumab（BMS-936564）／低用量シタラビン併用療法の非盲検ランダム化第1/2相臨床試験 | A Phase 1/2, Open-label Randomized Study of Ulocuplumab (BMS-936564) In Combination with Low Dose Cytarabine in Subjects with Newly Diagnosed Acute Myeloid Leukemia | ||
| BMS-936564の第1/2相臨床試験 | A Phase 1/2 study of Ulocuplumab (BMS-936564) | ||
（２）治験責任医師等に関する事項
（２）治験責任医師等に関する事項
| ブリストル・マイヤーズ スクイブ株式会社 | Bristol-Myers Squibb K.K. | ||
| 治験情報問合せ担当 | Clinical Trials Contact Personnel | ||
| 東京都千代田区大手町一丁目2 番1 号 | 1-2-1 Otemachi, Chiyoda-ku, Tokyo | ||
| 0120-093-507 | |||
| mg-jp-clinical_trial@bms.com | |||
| ブリストル・マイヤーズ スクイブ株式会社 | Bristol-Myers Squibb K.K. | ||
| 治験情報問合せ担当 | Clinical Trials Contact Personnel | ||
| 東京都千代田区大手町一丁目2 番1 号 | 1-2-1 Otemachi, Chiyoda-ku, Tokyo | ||
| 0120-093-507 | |||
| mg-jp-clinical_trial@bms.com | |||
| 2014年12月12日 |
（３）その他の試験等に従事する者に関する事項
（３）その他の試験等に従事する者に関する事項
（４）多施設共同試験等における治験責任医師等に関する事項など
（４）多施設共同試験等における治験責任医師等に関する事項など
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２ 試験等の目的及び内容並びにこれに用いる医薬品等の概要
２ 試験等の目的及び内容並びにこれに用いる医薬品等の概要
（１）試験等の目的及び内容
（１）試験等の目的及び内容
| 本試験の目的は新たに診断された急性骨髄性白血病患者を対象に、低用量シタラビンとの併用でulocuplumab(BMS-936564)の安全性及び有効性を評価することである。 | The purpose of this study is to determine the safety and effectiveness of ulocuplumab in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). | ||
| 1-2 | 1-2 | ||
| 2015年04月10日 | |||
| 2015年01月01日 | |||
| 2021年09月01日 | |||
| 126 | |||
| 介入研究 | Interventional | ||
評価項目分類：安全性試験及び有効性試験 介入方法：ランダム化割付 盲検：非盲検 主要目的：薬剤投与 |
Assessment Categories:Safty and Efficacy Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment |
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治療 |
treatment purpose |
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| / | 日本/アジア（日本以外）/北米/南米/欧州 | Japan/Asia except Japan/North America/South America/Europe | |
| / | 新たに診断された急性骨髄性白血病 |
Newly Diagnosed Acute Myeloid Leukemia (AML) |
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| / | 急性前骨髄球性白血病 |
Acute promyelocytic leukemia |
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| / | 18歳以上 |
18age old over |
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| / | 上限なし |
No limit |
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| / | 男性・女性 |
Both |
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| / | 急性骨髄性白血病 | Acute Myeloid Leukemia | |
| / | |||
| / | 試験対象薬剤等 一般的名称等：ulocuplumab(BMS-936564) 薬剤・試験薬剤：- 薬効分類コード：42- 腫瘍用薬 用法・用量、使用方法：通常、成人にはulocuplumab (BMS-936564)を1及び2コース目はDay 1、8及び15（28日／コース）、3コース目以降はDay 1及び8（28日／コース）に静脈内投与する。 一般的名称等：シタラビン 薬剤・試験薬剤：Cytarabine 薬効分類コード：422 代謝拮抗剤 用法・用量、使用方法：シタラビンは全コースのDay 1からDay 10まで20 mgを1日2回（40 mg／日）皮下投与する。 対象薬剤等 一般的名称等：- 薬剤・試験薬剤：- 薬効分類コード：--- その他 用法・用量、使用方法：- |
investigational material(s) Generic name etc : ulocuplumab(BMS-936564) INN of investigational material : - Therapeutic category code : 42- Antineoplastic agents Dosage and Administration for Investigational material : Ulocuplumab will be administered as a single IV infusion on Day 1, 8, and 15 of the first 2 cycles and on Day 1 and 8 of each Generic name etc : Cytarabine INN of investigational material : Cytarabine Therapeutic category code : 422 Antimetabolic agents Dosage and Administration for Investigational material : LDAC (20 mg BID [40 mg total daily dose]) will be subcutaneously administered on Day 1 - 10 for all cycles. control material(s) Generic name etc : - INN of investigational material : - Therapeutic category code : --- Other Dosage and Administration for Investigational material : - |
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| / | 安全性 有効性 第1相試験：安全性及び忍容性 第2相試験：完全寛解(CR)、血球数が未回復な完全寛解(CRi)、完全寛解の割合( CR/CRi) 第1相試験：1コース目に発現したDLT、並びに併用療法による治験薬投与期及び30日間の追跡期に発現したAE、グレード3以上のAE、中止に至ったAE、SAE、死亡及び臨床検査値異常を本試験の主要評価項目とする。AEはNCI CTCAE v4.03に従ってグレード分類する。 第2相試験：完全寛解率に基づき最良総合効果を判定する。 |
safety efficacy Phase 1:To assess the safety and tolerability Phase 2 :(expansion cohort) Complete Remission (CR), Complete Remission with incomplete blood count recovery (CRi), Rate of Complete Remission (CR/CRi) Phase 1:Number of patients experiencing a ulocuplumab-related dose limiting toxicity (DLT) during the DLT evaluation period based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) [ Time Frame: Up to 30 days after discontinuation of treatment ] Phase 2:Best overall response based on the Rate of Complete Remission (CR/CRi) |
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| / | 安全性 有効性 薬物動態 ファーマコゲノミクス 第2相試験： 1.安全性及び耐容性 2.薬物動態 3.免疫原性 4.ECGに対する影響 5.全寛解率及び完全奏効持続期間 6.LDAC単剤投与群における有効性及びヒストリ化るコントロールとの比較 7.全生存期間 第2相試験： 1: 投与終了30日後までの有害事象を収集する。 2: Cmax, Ctrough, Tmax, AUC(0-T), AUC(TAU), AUC(INF), T-HALF, CLTおよびVss 3: ulocuplumab(BMS-936564)に対する抗薬物抗体の発現 4: QTcF, QT, QRS, PR, 心拍数, QTcB及びそれぞれのベースラインからの変化量 5: 全寛解（OR=PR+CR+Cri）、CR又はCRiの初回確認日から死亡日、再発日又は感懐中の新たな療法開始日までの期間 6: CR/CRi率、OR率及び奏効期間 7: 投与開始日から死亡日までの期間 |
safety efficacy pharmacokinetics pharmacogenomics Phase 2: 1.Safety and tolerability 2.pharmacokinetic parameter(PK) 3.anti-drug antibody(ADA) 4.The effect of ulocuplumab on ECG intervals 5.Overall remission as well as duration of complete remission 6.Efficacy in subject treated with LDAC alone, to compare with historical controls of LDAC 7.Overall Survival(OS) Phase 2: 1:Time Frame: Up to 30 days after discontinuation of treatment 2:Cmax, Ctrough, Tmax, AUC(0-T), AUC(TAU), AUC(INF), T-HALF, CLT and Vss 3: ADA positive for ulocuplumab 4: QTcF, QT, QRS, PR, heart rate and QTcB as well as the associated changes from base line 5: Overall Remission (OR=PR+CR+Cri),the time from the date of first documented CR or CRi to the date of death, relapse, or initiation of alternative therapy while in remission 7:The time between the first date of treatment and the date of death due to any cause |
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（２）試験等に用いる医薬品等の概要
（２）試験等に用いる医薬品等の概要
| 医薬品 | medicine | |||
| ulocuplumab(BMS-936564) | ulocuplumab(BMS-936564) | |||
| - | - | |||
| 42- 腫瘍用薬 | 42- Antineoplastic agents | |||
| 通常、成人にはulocuplumab (BMS-936564)を1及び2コース目はDay 1、8及び15（28日／コース）、3コース目以降はDay 1及び8（28日／コース）に静脈内投与する。 | Ulocuplumab will be administered as a single IV infusion on Day 1, 8, and 15 of the first 2 cycles and on Day 1 and 8 of each | |||
| シタラビン | Cytarabine | |||
| Cytarabine | Cytarabine | |||
| 422 代謝拮抗剤 | 422 Antimetabolic agents | |||
| シタラビンは全コースのDay 1からDay 10まで20 mgを1日2回（40 mg／日）皮下投与する。 | LDAC (20 mg BID [40 mg total daily dose]) will be subcutaneously administered on Day 1 - 10 for all cycles. | |||
| - | - | |||
| - | - | |||
| --- その他 | --- Other | |||
| - | - | |||
３ 試験等の実施状況の確認に関する事項
３ 試験等の実施状況の確認に関する事項
（１）監査の実施予定
（１）監査の実施予定
（２）試験等の進捗状況
（２）試験等の進捗状況
| 参加募集終了 | completed | |
| / | 試験中止（恒久的） |
terminated |
４ 試験等の対象者に健康被害が生じた場合の補償及び医療の提供に関する事項
４ 試験等の対象者に健康被害が生じた場合の補償及び医療の提供に関する事項
５ 依頼者等に関する事項
５ 依頼者等に関する事項
（１）依頼者等に関する事項
（１）依頼者等に関する事項
| ブリストル・マイヤーズ スクイブ株式会社 | ||
| Bristol-Myers Squibb K.K. | ||
| - | ||
| - | ||
（２）依頼者以外の企業からの研究資金等の提供
（２）依頼者以外の企業からの研究資金等の提供
| - | - | |
| - | - |
６ IRBの名称等
６ IRBの名称等
| 東京都立駒込病院 治験審査委員会 | Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital IRB | |
| 東京都文京区本駒込3-18-22 | 3-18-22 Honkomagome, Bunkyo-ku, Tokyo | |
| 承認 | approved | |
７ その他の事項
７ その他の事項
（１）試験等の対象者等への説明及び同意に関する事項
（１）試験等の対象者等への説明及び同意に関する事項
（２）他の臨床研究登録機関への登録
（２）他の臨床研究登録機関への登録
| 有 | presence | |
| NCT02305563 | ||
| ClinicalTrials.gov | ClinicalTrials.gov | |
| JapicCTI-152802 | ||
（３）臨床研究を実施するに当たって留意すべき事項
（３）臨床研究を実施するに当たって留意すべき事項
（５）全体を通しての補足事項等
（５）全体を通しての補足事項等
| CA212-016 試験実施地域 : 米国、日本、韓国、台湾、香港、カナダ、ブラジル、ルーマニア、フランス、イタリア、ロシア、イスラエル、及びポーランド 試験の目的 : 本試験の目的は新たに診断された急性骨髄性白血病患者を対象に、低用量シタラビンとの併用でulocuplumab(BMS-936564)の安全性及び有効性を評価することである。 関連ＩＤ名称 : ClinicalTrials.gov 関連ＩＤ番号 : NCT02305563 | CA212-016 Region : US, Japan, Korea, Taiwan, Hong Kong, Canada, Brazil, Rumania, France, Italy, Russia, Israel, Poland Objectives of the study : The purpose of this study is to determine the safety and effectiveness of ulocuplumab in combination with low dose cytarabine in the treatment of Newly Diagnosed Acute Myeloid Leukemia (AML). Related ID Name : ClinicalTrials.gov Related ID number : NCT02305563 | ||
| ClinicalTrials.gov | ClinicalTrials.gov | ||
| https://www.clinicaltrials.gov/ct2/show/NCT02305563?term=NCT02305563&rank=1 | |||
添付書類
添付書類
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添付書類（終了時（総括報告書の概要提出時）の添付書類）
添付書類（終了時（総括報告書の概要提出時）の添付書類）
| https://storage.googleapis.com/ctgov2-large-docs/63/NCT02305563/Prot_000.pdf | |||
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| 2017年07月27日 | |||
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