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骨髄線維症患者におけるルキソリチニブの有無による CPI-0610 の第 2 相試験

2026年5月8日 更新者：Constellation Pharmaceuticals

BETタンパク質の低分子阻害剤であるCPI-0610の第1/2相試験：第1相（血液悪性腫瘍患者におけるCPI-0610の用量漸増）および第2相（患者におけるルキソリチニブの有無にかかわらずCPI-0610の用量拡大）骨髄線維症および本態性血小板減少症を伴う)

第 1 相パート (完了): 治療歴のある急性白血病、骨髄異形成症候群、骨髄異形成/骨髄増殖性腫瘍、および骨髄線維症の患者における、ペラブレシブの非盲検逐次用量漸増試験。

第 2 相パート: 骨髄線維症患者におけるルキソリチニブ併用および非併用の CPI-0610 の非盲検試験。

CPI-0610 は、ブロモドメインおよび末端外 (BET) タンパク質の低分子阻害剤です。

調査の概要

状態

完了

条件

介入・治療

研究の種類

介入

入学 (実際)

336

段階

  • フェーズ2
  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • アメリカ
    • Arizona
      • Phoenix、Arizona、アメリカ、85054
        • Mayo Clinic Arizona
    • California
      • Los Angeles、California、アメリカ、90095
        • UCLA Medical Center
    • Florida
      • Jacksonville、Florida、アメリカ、32224
        • Mayo Clinic Jacksonville
    • Illinois
      • Chicago、Illinois、アメリカ、60611
        • Northwestern University - Lurie Comprehensive Cancer Center
    • Massachusetts
      • Boston、Massachusetts、アメリカ、02114
        • Massachusetts General Hospital Cancer Center
    • Michigan
      • Ann Arbor、Michigan、アメリカ、48109
        • University of Michigan Medical Center
    • Missouri
      • St Louis、Missouri、アメリカ、63110
        • Washington University School of Medicne Neuromuscular Division Department of Neurology Research
    • New York
      • New York、New York、アメリカ、10029
        • Icahn School of Medicine at Mount Sinai
      • New York、New York、アメリカ、10021
        • Memorial Sloan Kettering Cancer Center
      • New York、New York、アメリカ、10065
        • Weill Medical College and New York Presbyterian Hospital
    • Texas
      • Houston、Texas、アメリカ、77030
        • The University of Texas MD Anderson Cancer Center
    • Wisconsin
      • Milwaukee、Wisconsin、アメリカ、53226
        • Froedtert & Medical College of Wisconsin
  • イギリス
      • Belfast、イギリス、BT9 7AB
        • Belfast City Hospital
      • Cambridge、イギリス、CB2 0QQ
        • University of Cambridge
      • Cardiff、イギリス、CF14 4XW
        • University Hospital of Wales
      • Glasgow、イギリス、G12 0YN
        • Beatson West of Scotland Cancer Centre
      • London、イギリス、NW1 2PG
        • University College London Hospital's NHS foundation Trust
      • London、イギリス、SE1 9RT
        • Guys and St Thomas' Hospital - Haematology
      • Manchester、イギリス、M20 4BX
        • The Christie Hospital
    • Oxford
      • Headington、Oxford、イギリス、OX3 7LE
        • Oxford University Hospitals
  • イタリア
      • Florence、イタリア、50134
        • Azienda Ospedaliero-Universitaria Careggi
      • Novara、イタリア、28100
        • AOU Maggiore della Carita
    • Emilia-Romagna
      • Bologna、Emilia-Romagna、イタリア、40138
        • Institue of Hematology "L. and A. Seràgnoli"
      • Rimini、Emilia-Romagna、イタリア、47923
        • Servizio Sanitario Regionale Emilia-Romagna - Azienda Unita Sanitaria Locale (AUSL) di Rimini - Ospedale Infermi di Rimini
    • Liguria
      • Genoa、Liguria、イタリア、16132
        • AOU S.Martino, IRCCS, IST-Istituto Nazionale Ricerca Sul Can
    • Lombardy
      • Milan、Lombardy、イタリア、20122
        • Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda
      • Pavia、Lombardy、イタリア、27100
        • Irccs Policlinico San Matteo, Universita Degli Studi Di Pavi
      • Varese、Lombardy、イタリア、21100
        • Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fon
  • オランダ
    • Limburg
      • Maastricht、Limburg、オランダ、6229 HX
        • Maastricht University Medical Center
    • North Holland
      • Amsterdam、North Holland、オランダ、1081 HV
        • VUmcResearch B.V.
    • South Holland
      • Rotterdam、South Holland、オランダ、3015 AA
        • Erasmus Universitair Medisch Centrum Rotterdam
  • カナダ
    • Alberta
      • Edmonton、Alberta、カナダ、T6G 2G3
        • University of Alberta Hospital
    • British Columbia
      • Vancouver、British Columbia、カナダ、V6Z 2A5
        • St. Paul's Hospital
    • Ontario
      • Hamilton、Ontario、カナダ、L8V 5C2
        • Juravinski Cancer Centre
      • Toronto、Ontario、カナダ、M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montreal、Quebec、カナダ、H3T 1E2
        • Jewish General Hospital
  • ドイツ
    • North Rhine-Westphalia
      • Bonn、North Rhine-Westphalia、ドイツ、53127
        • Universitatsklinikum Bonn
    • Saxony
      • Leipzig、Saxony、ドイツ、04103
        • Universitätsklinikum Leipzig AöR
  • フランス
      • Paris、フランス、75010
        • CHU - Hopital Saint Louis - Centre D'Investigations Clinique
    • Gard
      • Nîmes、Gard、フランス、30029
        • Institut de cancérologie du Gard - Hematologie clinique
    • Haute-Garonne
      • Toulouse、Haute-Garonne、フランス、31059
        • CHRU de Lille - Hopital Claude Huriez
    • Hauts-de-France
      • Lille、Hauts-de-France、フランス、59037
        • CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang
    • Île-de-France Region
      • Villejuif、Île-de-France Region、フランス、94805
        • Institut Gustave Roussy
  • ベルギー
      • Antwerp、ベルギー、2060
        • ZNA Stuyvenberg Antwerpen
    • Viaams Braban
      • Leuven、Viaams Braban、ベルギー、3000
        • UZ Leuven - Campus Gasthuisberg
    • West-Vlaanderen
      • Bruges、West-Vlaanderen、ベルギー、8000
        • AZ Sint-Jan Burgge-Oostende AV- Campus Sint-Jan
  • ポーランド
    • Masovian Voivodeship
      • Warsaw、Masovian Voivodeship、ポーランド、02-776
        • Instytut Hematologii I Transfuzjologii W Warszawie
    • Pomeranian Voivodeship
      • Gdansk、Pomeranian Voivodeship、ポーランド、80-952
        • Uniwersyteckie Centrum Kliniczne

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

説明

包含基準:

フェーズ 2 パート: 以下のすべての基準を満たす MF の診断が確認された患者:

  • 顆粒球増殖因子の補助なしで、ANC ≥ 1 x 10^9/L
  • 末梢血芽球数
  • -ECOGパフォーマンスステータス≤2。
  • 適切な血液学的、腎臓、肝臓、および凝固検査室評価
  • BET阻害剤による前治療なし
  • 患者は、研究関連の手順を実行する前に、この研究に参加するために書面によるインフォームドコンセントを提供する必要があります。

アーム 1 および 2 については、次の基準を考慮する必要があります。

  • MFの診断が確定し、以下の基準をすべて満たす患者
  • Dynamic International Prognostic Sc​​oring System (DIPSS) リスク カテゴリが中級 2 以上
  • -コホート1Bおよび2BのMRIまたはCTによる脾臓容積≧450 cm^3またはRBC輸血依存性（1か月あたり平均2単位以上のRBC輸血として定義（合計6回を超えるRBC輸血）登録前の12週間）コホート 1A および 2A の場合)
  • -骨髄線維症症状評価フォームバージョン4.0（MFSAF v4.0）を使用して、少なくとも2つの症状が測定可能（スコア≥1）
  • -少なくとも14日間、血小板新生因子または輸血の助けを借りずに、血小板数≥75 x 10^9 / L
  • アーム (アーム 1): 以前に JAK 阻害剤で治療され、JAK 阻害剤に対して不耐性、抵抗性、難治性、または応答を失った; -治験薬の開始前2週間以内にJAK阻害剤を投与されていない、またはJAK阻害剤による治療を受ける資格がない
  • 併用アーム (アーム 2): ルキソリチニブの単剤投与を受けており、少なくとも 8 週間は安定した用量を使用しているが、ルキソリチニブによって十分に制御されていない疾患がある

アーム 3 (JAK 阻害剤ナイーブ) については、次の基準を考慮する必要があります。

  • MFの診断が確定し、以下の基準をすべて満たす患者
  • Dynamic International Prognostic Sc​​oring System (DIPSS) リスク カテゴリが中級 2 以上
  • -血小板数が100 x 10^9/L以上で、血小板新生因子または輸血の助けを借りていない
  • MRI/CTによる脾臓容積≧450cm^3
  • -骨髄線維症症状評価フォームバージョン4.0（MFSAF v4.0）を使用して、測定可能な少なくとも2つの症状（スコア≥3）または合計スコア≥10
  • JAKiによる前治療は許可されていません

アーム 4 (ET 拡張) については、次の基準を考慮する必要があります。

  • ETの確定診断を受けた患者
  • 以下の基準の少なくとも 1 つを満たすと定義される高リスク疾患:
  • 年齢 > 60 歳
  • -血小板数> 1500×10 ^ 9 / L（患者の疾患中の任意の時点で）
  • 以前に文書化された血栓症、紅斑痛、または片頭痛
  • -ETに関連する以前の出血
  • -6か月以上の薬物療法を必要とする糖尿病または高血圧

  • -2つ以上の症状があり、サイクル1の1日目の前の7日間で平均スコアが3以上、またはMPN SAFを使用してサイクル1の1日目の前の7日間で平均合計スコアが15以上

    • 血小板 > 600 × 10^9/L
    • HUに抵抗性または不寛容

除外基準:

  • -現在知られているヒト免疫不全ウイルス（HIV）、B型肝炎またはC型肝炎による活動性または慢性感染症。
  • -心機能障害または臨床的に重要な心疾患
  • Child-Pugh クラス B または C の患者
  • -CTCAEグレード> 1の未解決の吐き気、嘔吐、または下痢を含む、ペラブレシブおよび/またはルキソリチニブの吸収を大幅に変化させる可能性のある胃腸（GI）機能またはGI疾患の障害
  • -BET阻害剤による前治療。
  • 妊娠中または授乳中の女性
  • -研究への参加を危うくする可能性のある、その他の重篤なおよび/または制御されていない付随する病状
  • -この研究プロトコルを遵守したくない、または遵守できない患者。

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：非ランダム化
  • 介入モデル：並列代入
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Phase 1
Patients were enrolled in sequential cohorts (acute leukemia, including acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and acute undifferentiated or biphenotypic leukemia; chronic myelogenous leukemia (CML) in blast crisis; myelodysplastic syndrome (MDS); myelodysplastic/myeloproliferative neoplasms (MDS/MPN); or myelofibrosis (MF)) and received escalating doses of pelabresib (CPI-0610).
薬：Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
他の名前：
  • CPI-0610
  • DAK539
実験的：Phase 2 (Arm 1): Prior JAKi Monotherapy Arm (MF patients treated with pelabresib alone)
  • Cohort 1A: Was open to patients with MF who were Transfusion Dependent (TD) and who had previously been treated with a JAKi and were intolerant, resistant, refractory, or had lost response to the JAKi, or were ineligible to be treated with a JAKi (pelabresib (CPI-0610) alone).
  • Cohort 1B: Was open to patients with MF who were not TD and who had previously been treated with a JAKi and were intolerant, resistant, refractory, or had lost response to the JAKi, or were ineligible to be treated with a JAKi (pelabresib (CPI-0610) alone).
薬：Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
他の名前：
  • CPI-0610
  • DAK539
実験的：Phase 2 (Arm 2): Prior JAKi Combination Arm
  • Cohort 2A: Was open to patients with MF who were Transfusion Dependent (TD) and were taking ruxolitinib but had disease that was not adequately controlled by ruxolitinib (pelabresib (CPI-0610) + Ruxolitinib).
  • Cohort 2B: Was open to patients with MF who were not TD and were taking ruxolitinib but had disease that was not adequately controlled by ruxolitinib (pelabresib (CPI-0610) + Ruxolitinib).
薬：Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
他の名前：
  • CPI-0610
  • DAK539
薬：Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
実験的：Phase 2 (Arm 3): JAKi Naïve Combination Arm
Was open to patients with MF who had not previously received a JAKi (pelabresib (CPI-0610) + Ruxolitinib).
薬：Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
他の名前：
  • CPI-0610
  • DAK539
薬：Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
実験的：Phase 2 (Arm 4): Essential Thrombocythemia (ET) Monotherapy Arm
Was open to high-risk patients with ET who were resistant or intolerant to hydroxyurea (HU) (pelabresib (CPI-0610) alone).
薬：Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
他の名前：
  • CPI-0610
  • DAK539

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
時間枠：Up to 21 days
A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed by the Investigator as unrelated to disease progression, intercurrent illness, or concomitant medications that occurred within the first cycle of treatment (21-day cycle) with pelabresib (CPI-0610), and that met any of the criteria specified in the protocol.
Up to 21 days
Phase 2 (Cohorts 1B, 2B, and Arm 3): Number of Participants With Splenic Response Rate (SVR35) at Week 24
時間枠：Week 24 (Cycle 9 Day 1)
Splenic Response Rate (SVR35) at Week 24 was defined as the proportion of participants who demonstrated a reduction of at least 35% in spleen size from baseline, as measured by imaging techniques (MRI or CT), following 24 weeks of treatment.
Week 24 (Cycle 9 Day 1)
Phase 2 (Cohorts 1A and 2A): Number of Participants Enrolled as Transfusion Dependent (TD) With Conversion Rate From Red Blood Cell (RBC) Transfusion Dependence (TD) to Transfusion Independence (TI)
時間枠：Any 12 consecutive weeks (rolling window) during active treatment with pelabresib (CPI-0610), from first dose through treatment discontinuation (up to approximately 8 years for Phase II)
Conversion rate was defined as the proportion of participants who converted from transfusion dependence (TD) to transfusion independence (TI). TD was characterized by receiving an average of at least 2 units of red blood cell (RBC) transfusions per month-amounting to a minimum of 6 units over the 12 weeks prior to enrollment-while TI was defined as the absence of RBC transfusions during any consecutive 12-week period.
Any 12 consecutive weeks (rolling window) during active treatment with pelabresib (CPI-0610), from first dose through treatment discontinuation (up to approximately 8 years for Phase II)
Phase 2 (Arm 4): Number of Participants With Complete Hematological Response (CHR) Rate
時間枠：Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)
Complete Hematological Response (CHR) Rate was defined as the proportion of participants who fulfilled the criteria for CHR, based on the modified European LeukemiaNet (ELN) guidelines (Barosi et al 2009): platelet count ≤400 × 10⁹/L, white blood cell (WBC) count ≤10 × 10⁹/L, confirmation of laboratory values after one treatment cycle, and normal spleen size determined by palpation or imaging.
Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)

二次結果の測定

結果測定
メジャーの説明
時間枠
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
時間枠：Up to approximately 6 months
The distribution of adverse events was performed through the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs), based on the monitoring of relevant clinical and laboratory safety parameters. Treatment-emergent adverse events (TEAEs) in this study were defined as events that began after the first dose of study treatment and continued until 30 days after the last dose, or events that were present prior to the first dose and increased in severity based on preferred term within 30 days following the last dose of pelabresib (CPI-0610).
Up to approximately 6 months
Phase 2 (All Arms): Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
時間枠：Up to approximately 387 weeks
The distribution of adverse events was performed through the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs), based on the monitoring of relevant clinical and laboratory safety parameters. Treatment-emergent adverse events (TEAEs) in this study were defined as events that began after the first dose of study treatment and continued until 30 days after the last dose, or events that were present prior to the first dose and increased in severity based on preferred term within 30 days following the last dose of pelabresib (CPI-0610).
Up to approximately 387 weeks
Phase 2 (All Arms): Symptom Improvement From the Patient Global Impression of Change (PGIC) at 12 and 24 Weeks
時間枠：Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)
The Patient Global Impression of Change (PGIC) was a single-question, patient-reported assessment that asked individuals to rate their overall change in myeloproliferative neoplasm (MPN) symptoms since starting study treatment. The participants selected one of seven options, ranging from 'Very much improved' to 'Very much worse'. 'No Change from Baseline' indicated stable symptoms (no improvement or worsening), negative change from Baseline indicated a reduction in symptom severity (improvement), and positive change from Baseline indicated an increase in symptom severity (worsening).
Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)
Phase 2 (Arms 1, 2 and 3): Percent Change From Baseline in Total Symptom Score (TSS) From the Myelofibrosis Symptom Assessment Form (MFSAF v4.0) at 12 and 24 Weeks
時間枠：Baseline, Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)
The MFSAF (Myelofibrosis Symptom Assessment Form) was completed by participants every day for 7 days before Day 1 of each treatment cycle, including the 7 days before starting Cycle 1. It used a 24-hour recall format, asking participants to rate the worst severity of seven symptoms (fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety, and bone pain) during the past 24 hours. Each symptom was rated on a scale from 0 (Absent) to 10 (Worst Imaginable). The Total Symptom Score (TSS) was the sum of 7 symptoms (range: 0-70). 'No Change from Baseline' indicated stable symptoms (no improvement or worsening), negative change from Baseline indicated a reduction in symptom severity (improvement), and positive change from Baseline indicated an increase in symptom severity (worsening).
Baseline, Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)
Phase 2 (Arms 1, 2 and 3): Number of Participants Who Achieved a ≥ 50% Reduction in Total Symptom Score (TSS) at 12 and 24 Weeks
時間枠：Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)
The proportion of study participants who experienced a reduction of at least 50% in their Total Symptom Score (TSS), as assessed using the Myelofibrosis Symptom Assessment Form (MFSAF v4.0), was evaluated at both 12 and 24 weeks relative to their baseline score.
Week 12 (Cycle 5 Day 1), Week 24 (Cycle 9 Day 1)
Phase 2 (Arms 1, 2 and 3): Number of Participants With Overall Splenic Response Rate (Overall SVR35)
時間枠：Through Phase II completion, an average of 6 years
Overall Splenic Response Rate (SVR35) was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as measured by imaging (MRI or CT), at any point between Cycle 1 Day 1 and the End of Study Visit, whichever occurred first.
Through Phase II completion, an average of 6 years
Phase 2 (Arms 1, 2 and 3): Duration of Overall Splenic Response (Overall SVR35)
時間枠：From first onset of splenic response until loss of response, assessed up to approximately 6 years
Duration of Overall Splenic Response (overall SVR35) was defined as the time from the first occurrence of a at least 35% reduction in spleen volume from baseline until the earliest of the following: a reduction of less than 35% from baseline combined with an increase of more than 25% from the nadir in spleen volume (as measured by MRI or CT), or death. The nadir was defined as the lowest spleen volume recorded after baseline and up to the evaluation point at which the initial splenic response was achieved.
From first onset of splenic response until loss of response, assessed up to approximately 6 years
Phase 2 (Cohorts 1A and 2A): Number of Participants With Splenic Response Rate (SVR35) at 12 and 24 Weeks
時間枠：Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)
Splenic Response Rate (SVR35) at 12 and 24 weeks was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as determined by imaging (MRI or CT), following 12 and 24 weeks of treatment, respectively.
Week 12 (Cycle 5 Day 1), Week 24 weeks (Cycle 9 Day 1)
Phase 2 (Cohorts 1A and 2A): Duration of Red Blood Cell (RBC) Transfusion Independence (TI) in Participants Who Enroll as Transfusion Dependent (TD)
時間枠：From first onset of TI to earliest onset of loss of TI, assessed up to approximately 6 years
Duration of Red Blood Cell (RBC) Transfusion Independence (TI) was defined as the longest continuous period during which participants, having achieved at least 12 weeks of transfusion independence, remained free from RBC transfusions.
From first onset of TI to earliest onset of loss of TI, assessed up to approximately 6 years
Phase 2 (Cohorts 1A and 2A): Early Anemic Response Rate in Participants Who Enroll as Transfusion Dependent (TD)
時間枠：Through Phase II completion, an average of 6 years
Early anemic response rate was defined as the proportion of participants who achieved an average increase of at least 1 g/dL in hemoglobin concentration over any rolling 8-week (56-day) period following baseline. This calculation was performed after applying the 14/3 day rule, which stipulates that hemoglobin measurements must be spaced at least 14 days apart, and that at least 3 such measurements are required within the 8-week window to ensure a reliable average. Importantly, this increase had to occur without any red blood cell (RBC) transfusions during the treatment period and up to the time of the latest hemoglobin assessment for each patient.
Through Phase II completion, an average of 6 years
Phase 2 (Cohorts 1B, 2B, and Arm 3): Number of Participants With Splenic Response Rate (SVR35) at 12 Weeks
時間枠：Week 12 (Cycle 5 Day 1)
Splenic Response Rate (SVR35) at Week 12 was defined as the proportion of participants who achieved a reduction of at least 35% in spleen size from baseline, as measured by imaging (MRI or CT), following 12 weeks of treatment.
Week 12 (Cycle 5 Day 1)
Phase 2 (Cohorts 1B, 2B, and Arm 3): Anemic Response Rate in Participants Who Enroll as Non-transfusion-dependent (Non-TD)
時間枠：Through Phase II completion, an average of 6 years
Anemic response was defined as a sustained average increase in hemoglobin concentration of at least 1.5 g/dL over any rolling 12-week (84-day) period following baseline. This calculation excluded periods involving red blood cell (RBC) transfusions and was performed after applying the 14/3-day rule for valid hemoglobin assessments. The response had to be maintained through to the most recent available hemoglobin measurement for each patient.
Through Phase II completion, an average of 6 years
Phase 2 (Arm 4): Percentage of Participants Who Achieve a ≥50% Reduction From Baseline in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Score
時間枠：Baseline, 12 weeks (Cycle 5, Day 1), 24 weeks (Cycle 9, Day 1)
The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a patient-reported questionnaire designed to measure symptom burden in participants with myeloproliferative neoplasms (MPNs). Participants rate the severity of several symptoms (such as fatigue, night sweats, itching, abdominal discomfort, bone pain, early satiety, and others) over the past 24 hours. Each symptom is scored on a scale from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be). The total score is the sum of all individual symptom scores, providing an overall measure of symptom burden. A 50% reduction in the MPN-SAF total score at 12 or 24 weeks means the patient's overall symptom burden has improved by half compared to their baseline (pre-treatment) score.
Baseline, 12 weeks (Cycle 5, Day 1), 24 weeks (Cycle 9, Day 1)
Phase 2 (Arm 4): Partial Hematological Response Rate (PHR)
時間枠：Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)

Partial Hematological Response Rate (PHR) was defined as the proportion of participants who met the following criteria over two consecutive cycles up to the last administration of study treatment:

  • Platelet count > 400-600 x 10^9/L
  • WBC count within normal range (i.e., ≤ 10 x 10^9/L)
  • Laboratory results confirmed after 1 cycle (after 3weeks)
Over 2 consecutive cycles (rolling window) (1 cycle = 21 days)
Phase 2 (Arm 4): Overall Hematological Response Rate (OHR)
時間枠：Through Phase II completion, an average of 6 years
Confirmed Overall Hematological Response (OHR) Rate was defined as the proportion of participants with either a confirmed complete or a partial hematological response at any time.
Through Phase II completion, an average of 6 years
Phase 2 (Arm 4): Duration of Overall Hematological Response Rate (OHR)
時間枠：Through Phase II completion, an average of 6 years
Duration of Overall Hematological Response (OHR) Rate was defined as the time from when the overall hematological response was first met until the time at which the overall hematological response was lost, i.e., the criteria for an overall hematological response (CHR or PHR) were not observed or death occurred, whichever came first.
Through Phase II completion, an average of 6 years
Phase 2 (Arm 4): Rate of Hemorrhagic and Thromboembolic (TE) Events
時間枠：Through Phase II completion, an average of 6 years
Rate of hemorrhagic and thromboembolic (TE) events was defined as the proportion of participants with hemorrhagic or thromboembolic events throughout the study.
Through Phase II completion, an average of 6 years
Phase 2 (All Arms): Maximum Observed Plasma Concentration (Cmax) of Pelabresib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (All Arms): Time to Reach Maximum Concentration (Tmax) of Pelabresib
時間枠：Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (All Arms): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Pelabresib
時間枠：Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (All Arms): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Pelabresib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (All Arms): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Pelabresib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (All Arms): Time of Last Measurable Concentration (Tlast) of Pelabresib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on Pelabresib plasma concentrations and actual sampling time points.

Tlast was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2A): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2A): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2A): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib
時間枠：Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2A): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2A): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2B): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2B): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2B): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2B): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 2 - Cohort 2B): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 3): Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Cmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 3): Time to Reach Maximum Concentration (Tmax) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Tmax was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 3): Predose (Trough) Concentration at the End of a Dosing Interval (Ctrough) of Ruxolitinib
時間枠：Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

Ctrough was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (predose, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 3): Area Under the Concentration-Time Curve From Time Zero to the Last Observed Concentration (AUClast) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUClast was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.
Phase 2 (Arm 3): Area Under the Concentration-Time Curve From Time Zero to 8 Hours Post-dose at Steady State (AUC0-8,ss) of Ruxolitinib
時間枠：Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

Pharmacokinetic (PK) parameters were calculated based on ruxolitinib plasma concentrations and actual sampling time points.

AUC0-8,ss was listed and summarized using descriptive statistics.
Cycle 1 Day 14 (30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 8 hours post-dose). 1 cycle = 21 days.

その他の成果指標

結果測定
時間枠
フェーズ 2 (アーム 1、2、および 3): 応答カテゴリ率の評価
時間枠：24 週間後の国際ワーキング グループ - 骨髄増殖性腫瘍の研究と治療 (IWG-MRT) 基準による反応率
24 週間後の国際ワーキング グループ - 骨髄増殖性腫瘍の研究と治療 (IWG-MRT) 基準による反応率
フェーズ 2 (アーム 1、2、および 3): RBC 輸血率と RBC 輸血依存率を評価します。
時間枠：対象月あたりの RBC 単位の平均数、最大 24 週間およびそれ以降
対象月あたりの RBC 単位の平均数、最大 24 週間およびそれ以降

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Constellation Pharmaceuticals

協力者

The Leukemia and Lymphoma Society

捜査官

  • スタディディレクター：Novartis Pharmaceuticals、Novartis Pharmaceuticals

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2014年7月16日

一次修了 (実際)

2025年1月9日

研究の完了 (実際)

2025年1月9日

試験登録日

最初に提出

2014年6月5日

QC基準を満たした最初の提出物

2014年6月5日

最初の投稿 (推定)

2014年6月9日

学習記録の更新

投稿された最後の更新 (実際)

2026年6月4日

QC基準を満たした最後の更新が送信されました

2026年5月8日

最終確認日

2026年4月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • 0610-02
  • 2018-000579-34 (EudraCT番号)
  • CDAK539A12201 (その他の識別子：Novartis)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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この試験データの入手可能性は、www.clinicalstudydatarequest.com に記載されている基準とプロセスに従っています。

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

米国で製造され、米国から輸出された製品。

いいえ

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