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Исследование фазы 2 CPI-0610 с руксолитинибом и без него у пациентов с миелофиброзом

8 мая 2026 г. обновлено: Constellation Pharmaceuticals

Исследование фазы 1/2 CPI-0610, низкомолекулярного ингибитора белков BET: фаза 1 (повышение дозы CPI-0610 у пациентов с гематологическими злокачественными новообразованиями) и фаза 2 (увеличение дозы CPI-0610 с руксолитинибом и без него у пациентов) При миелофиброзе и эссенциальной тромбоцитопении)

Часть фазы 1 (полная): открытое исследование с последовательным повышением дозы пелабресиба у пациентов с ранее леченным острым лейкозом, миелодиспластическим синдромом, миелодиспластическими/миелопролиферативными новообразованиями и миелофиброзом.

Фаза 2, часть: открытое исследование CPI-0610 с руксолитинибом и без него у пациентов с миелофиброзом.

CPI-0610 представляет собой низкомолекулярный ингибитор бромодоменных и экстратерминальных (BET) белков.

Обзор исследования

Статус

Завершенный

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Действительный)

336

Фаза

  • Фаза 2
  • Фаза 1

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

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

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

18 лет и старше (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Описание

Критерии включения:

Фаза 2: пациенты с подтвержденным диагнозом МФ, отвечающие всем следующим критериям:

  • ANC ≥ 1 x 10 ^ 9 / л без помощи факторов роста гранулоцитов
  • Подсчет бластов в периферической крови
  • Состояние работоспособности по ECOG ≤ 2.
  • Адекватные гематологические, почечные, печеночные и коагуляционные лабораторные оценки
  • Без предварительного лечения ингибитором BET
  • Пациенты должны дать письменное информированное согласие на участие в этом исследовании перед выполнением любой процедуры, связанной с исследованием.

Для ветвей 1 и 2 следует учитывать следующие критерии:

  • Пациенты с подтвержденным диагнозом MF, которые соответствуют всем следующим критериям
  • Динамическая международная система прогностической оценки (DIPSS) категория риска промежуточный-2 или выше
  • Объем селезенки ≥ 450 см ^ 3 по данным МРТ или КТ для когорт 1B и 2B ИЛИ зависит от переливания эритроцитов (определяется как среднее ≥ 2 единиц переливаний эритроцитов в месяц (всего более 6 переливаний эритроцитов) за 12 недель до включения для когорт 1А и 2А)
  • По крайней мере 2 симптома поддаются измерению (оценка ≥ 1) с использованием формы оценки симптомов миелофиброза версии 4.0 (MFSAF v4.0)
  • Количество тромбоцитов ≥ 75 x 10 ^ 9 / л без помощи тромбопоэтических факторов или трансфузий в течение как минимум 14 дней.
  • Группа (группа 1): ранее леченные ингибитором JAK и имеющие непереносимость, резистентность, рефрактерность или потерю ответа на ингибитор JAK; не получали ингибитор JAK в течение 2 недель до начала приема исследуемого препарата или не имеют права на лечение ингибитором JAK
  • Комбинированная группа (группа 2): пациенты должны получать монотерапию руксолитинибом и принимать стабильную дозу в течение как минимум 8 недель, но иметь заболевание, которое не контролируется руксолитинибом должным образом.

Для группы 3 (непринимавшие ингибиторы JAK) следует учитывать следующие критерии:

  • Пациенты с подтвержденным диагнозом MF, которые соответствуют всем следующим критериям
  • Динамическая международная система прогностической оценки (DIPSS) категория риска промежуточный-2 или выше
  • Количество тромбоцитов ≥ 100 x 10^9/л без помощи тромбопоэтических факторов или трансфузий
  • Объем селезенки ≥ 450 см^3 по данным МРТ/КТ
  • По крайней мере, 2 измеримых симптома (оценка ≥ 3) или общий балл ≥ 10 с использованием формы оценки симптомов миелофиброза версии 4.0 (MFSAF v4.0)
  • Предварительное лечение JAKi не допускается.

Для плеча 4 (расширение ET) следует учитывать следующие критерии:

  • Пациенты с подтвержденным диагнозом ЭТ
  • Заболевание высокого риска, определяемое как отвечающее хотя бы одному из следующих критериев:
  • Возраст > 60 лет
  • Количество тромбоцитов > 1500 × 10^9/л (в любой момент болезни пациента)
  • Ранее подтвержденный тромбоз, эритромелалгия или мигрень
  • Предшествующее кровотечение, связанное с ЭТ
  • Диабет или гипертония, требующие фармакологической терапии в течение > 6 мес.

  • Иметь ≥2 симптомов со средним баллом ≥ 3 за 7-дневный период до цикла 1, день 1 или средний общий балл ≥15 за 7-дневный период до цикла 1, день 1 с использованием MPN SAF

    • Тромбоциты > 600 × 10^9/л
    • Устойчивость или непереносимость HU

Критерий исключения:

  • Текущая известная активная или хроническая инфекция вирусом иммунодефицита человека (ВИЧ), гепатитом В или гепатитом С.
  • Нарушение функции сердца или клинически значимые заболевания сердца
  • Пациенты с классом B или C по Чайлд-Пью
  • Нарушение функции желудочно-кишечного тракта (ЖКТ) или заболевание ЖКТ, которое может значительно изменить абсорбцию пелабресиба и/или руксолитиниба, включая любую непреодолимую тошноту, рвоту или диарею степени >1 по СТСАЕ
  • Предварительное лечение ингибитором БЭТ.
  • Беременные или кормящие женщины
  • Любое другое сопутствующее тяжелое и/или неконтролируемое сопутствующее заболевание, которое может поставить под угрозу участие в исследовании.
  • Пациенты, не желающие или неспособные соблюдать этот протокол исследования.

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Нерандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: 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).
Лекарство: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Другие имена:
  • CPI-0610
  • ДАК539
Экспериментальный: 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).
Лекарство: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Другие имена:
  • CPI-0610
  • ДАК539
Экспериментальный: 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).
Лекарство: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Другие имена:
  • CPI-0610
  • ДАК539
Лекарство: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Экспериментальный: 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).
Лекарство: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Другие имена:
  • CPI-0610
  • ДАК539
Лекарство: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Экспериментальный: 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).
Лекарство: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Другие имена:
  • CPI-0610
  • ДАК539

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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)
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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.

Другие показатели результатов

Мера результата
Временное ограничение
Фаза 2 (Руки 1, 2 и 3): Оценить частоту ответов категории
Временное ограничение: Скорость ответа по критериям Международной рабочей группы по исследованию и лечению миелопролиферативных новообразований (IWG-MRT) через 24 недели
Скорость ответа по критериям Международной рабочей группы по исследованию и лечению миелопролиферативных новообразований (IWG-MRT) через 24 недели
Фаза 2 (группы 1, 2 и 3): оценить скорость переливания эритроцитов и степень зависимости от переливания эритроцитов
Временное ограничение: Среднее количество единиц эритроцита на одного субъекта в месяц, до 24 недель и более
Среднее количество единиц эритроцита на одного субъекта в месяц, до 24 недель и более

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Constellation Pharmaceuticals

Соавторы

The Leukemia and Lymphoma Society

Следователи

  • Директор по исследованиям: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Публикации и полезные ссылки

Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.

Общие публикации

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

16 июля 2014 г.

Первичное завершение (Действительный)

9 января 2025 г.

Завершение исследования (Действительный)

9 января 2025 г.

Даты регистрации исследования

Первый отправленный

5 июня 2014 г.

Впервые представлено, что соответствует критериям контроля качества

5 июня 2014 г.

Первый опубликованный (Оцененный)

9 июня 2014 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

4 июня 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

8 мая 2026 г.

Последняя проверка

1 апреля 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 0610-02
  • 2018-000579-34 (Номер EudraCT)
  • CDAK539A12201 (Другой идентификатор: Novartis)

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Описание плана IPD

Novartis стремится предоставлять квалифицированным внешним исследователям доступ к данным на уровне пациентов и подтверждающим клиническим документам из соответствующих исследований. Эти запросы рассматриваются и одобряются независимой экспертной комиссией на основании научной значимости. Все предоставленные данные анонимизированы в целях соблюдения конфиденциальности пациентов, принявших участие в исследовании, в соответствии с применимыми законами и правилами.

Доступность данных этого исследования соответствует критериям и процессу, описанным на сайте www.clinicalstudydatarequest.com.

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

продукт, произведенный в США и экспортированный из США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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