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골수 섬유증 환자에서 Ruxolitinib을 병용하거나 사용하지 않는 CPI-0610의 2상 연구

2026년 5월 8일 업데이트: Constellation Pharmaceuticals

BET 단백질의 소분자 억제제인 ​​CPI-0610의 1/2상 연구: 1상(혈액암 환자에서 CPI-0610의 용량 증량) 및 2상(환자에서 Ruxolitinib 유무에 따른 CPI-0610의 용량 증량) 골수 섬유증 및 본태성 혈소판 감소증 동반)

1상 부분(완전): 이전에 치료를 받은 급성 백혈병, 골수이형성 증후군, 골수이형성/골수증식성 신생물 및 골수 섬유증 환자를 대상으로 한 펠라브레시브의 공개 라벨 순차적 용량 증량 연구.

2상 부분: 골수 섬유증 환자에서 Ruxolitinib을 포함하거나 포함하지 않는 CPI-0610의 공개 라벨 연구.

CPI-0610은 브로모도메인 및 BET(extra-terminal) 단백질의 소분자 억제제입니다.

연구 개요

상태

완전한

정황

개입 / 치료

연구 유형

중재적

등록 (실제)

336

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

설명

포함 기준:

2상 부분: 다음 기준을 모두 충족하는 골수섬유화증 진단이 확인된 환자:

  • 과립구 성장 인자의 도움 없이 ANC ≥ 1 x 10^9/L
  • 말초 혈액 폭발 수
  • ECOG 수행 상태 ≤ 2.
  • 적절한 혈액학적, 신장, 간 및 응고 실험실 평가
  • BET 억제제로 사전 치료 없음
  • 환자는 연구 관련 절차를 수행하기 전에 이 연구에 참여하기 위해 서면 동의서를 제공해야 합니다.

Arm 1 및 2의 경우 다음 기준을 고려해야 합니다.

  • 다음 기준을 모두 충족하는 골수섬유화증 진단을 받은 환자
  • DIPSS(Dynamic International Prognostic Scoring System) 위험 범주 중급 2 이상
  • 코호트 1B 및 2B 또는 RBC 수혈 의존형(등록 전 12주 동안 매달 평균 ≥2 단위의 RBC 수혈(적혈구 수혈 총 6회 이상)로 정의됨)에 대해 MRI 또는 ​​CT에서 비장 부피 ≥ 450 cm^3 코호트 1A 및 2A의 경우)
  • 골수 섬유증 증상 평가 양식 버전 4.0(MFSAF v4.0)을 사용하여 측정 가능한 최소 2개의 증상(Score ≥ 1)
  • 최소 14일 동안 혈전 생성 인자 또는 수혈 없이 혈소판 수 ≥ 75 x 10^9/L
  • 아암(Arm 1): 이전에 JAK 억제제로 치료를 받았고 JAK 억제제에 대한 불내성, 저항성, 불응성 또는 상실된 반응 연구 약물 시작 전 2주 이내에 JAK 억제제를 투여받지 않았거나 JAK 억제제로 치료받을 자격이 없는 경우
  • 조합군(군 2): 단일제제인 룩솔리티닙을 투여받았고 최소 8주 동안 안정적인 용량을 사용해야 하지만 룩솔리티닙으로 적절하게 조절되지 않는 질병이 있어야 합니다.

3군(JAK 억제제 나이브)의 경우 다음 기준을 고려해야 합니다.

  • 다음 기준을 모두 충족하는 골수섬유화증 진단을 받은 환자
  • DIPSS(Dynamic International Prognostic Scoring System) 위험 범주 중급 2 이상
  • 혈소판 생성 인자 또는 수혈 없이 혈소판 수 ≥ 100 x 10^9/L
  • MRI/CT에서 비장 부피 ≥ 450 cm^3
  • 척수 섬유증 증상 평가 양식 버전 4.0(MFSAF v4.0)을 사용하여 측정 가능한 최소 2개의 증상(점수 ≥ 3) 또는 총 점수 ≥ 10
  • JAKi로 사전 치료 불가

Arm 4(ET 확장)의 경우 다음 기준을 고려해야 합니다.

  • ET 진단이 확정된 환자
  • 다음 기준 중 하나 이상을 충족하는 것으로 정의되는 고위험 질병:
  • 나이 > 60세
  • 혈소판 수 > 1500 × 10^9/L(환자 질병 중 임의의 시점)
  • 이전에 기록된 혈전증, 홍반통 또는 편두통
  • ET와 관련된 이전 출혈
  • 6개월 이상 약물치료가 필요한 당뇨병 또는 고혈압

  • MPN SAF를 사용하여 1주기 1일 전 7일 동안 평균 점수가 3점 이상이거나 주기 1일 1일 전 7일 동안 평균 총 점수가 15점 이상인 2개 이상의 증상이 있습니다.

    • 혈소판 > 600 × 10^9/L
    • HU에 저항성 또는 불내성

제외 기준:

  • 인간 면역결핍 바이러스(HIV), B형 간염 또는 C형 간염으로 현재 알려진 활동성 또는 만성 감염.
  • 심장 기능 장애 또는 임상적으로 중요한 심장 질환
  • Child-Pugh Class B 또는 C 환자
  • CTCAE 등급 >1인 해결되지 않은 메스꺼움, 구토 또는 설사를 포함하여 펠라브레시브 및/또는 룩솔리티닙의 흡수를 유의하게 변경할 수 있는 위장관(GI) 기능 장애 또는 GI 질환
  • BET 억제제로 사전 치료.
  • 임산부 또는 수유부
  • 연구 참여를 위태롭게 할 수 있는 기타 동시 중증 및/또는 통제되지 않는 수반되는 의학적 상태
  • 본 연구 프로토콜을 따르기를 꺼리거나 따를 수 없는 환자.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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).
의약품: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
다른 이름들:
  • CPI-0610
  • DAK539
실험적: 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).
의약품: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
다른 이름들:
  • CPI-0610
  • DAK539
실험적: 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).
의약품: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
다른 이름들:
  • CPI-0610
  • DAK539
의약품: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
실험적: 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).
의약품: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
다른 이름들:
  • CPI-0610
  • DAK539
의약품: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
실험적: 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).
의약품: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
다른 이름들:
  • CPI-0610
  • DAK539

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
기간: 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
기간: 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)
기간: 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
기간: 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)

2차 결과 측정

결과 측정
측정값 설명
기간
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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)
기간: 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
기간: 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)
기간: 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)
기간: 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
기간: 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)
기간: 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
기간: 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)
기간: 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)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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.

기타 결과 측정

결과 측정
기간
2단계(Arms 1, 2 및 3): 응답 범주 비율 평가
기간: 24주 후 International Working Group의 반응률 - IWG-MRT(Myeloproliferative Neoplasms Research and Treatment) 기준
24주 후 International Working Group의 반응률 - IWG-MRT(Myeloproliferative Neoplasms Research and Treatment) 기준
2상(1차, 2차, 3차): 적혈구 수혈률 및 RBC 수혈 의존도 평가
기간: 과목별 평균 RBC 단위 수, 최대 24주 및 그 이후
과목별 평균 RBC 단위 수, 최대 24주 및 그 이후

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Constellation Pharmaceuticals

협력자

The Leukemia and Lymphoma Society

수사관

  • 연구 책임자: Novartis Pharmaceuticals, Novartis Pharmaceuticals

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일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2014년 7월 16일

기본 완료 (실제)

2025년 1월 9일

연구 완료 (실제)

2025년 1월 9일

연구 등록 날짜

최초 제출

2014년 6월 5일

QC 기준을 충족하는 최초 제출

2014년 6월 5일

처음 게시됨 (추정된)

2014년 6월 9일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 6월 4일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 5월 8일

마지막으로 확인됨

2026년 4월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • 0610-02
  • 2018-000579-34 (EudraCT 번호)
  • CDAK539A12201 (기타 식별자: Novartis)

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이 시험 데이터 가용성은 www.clinicalstudydatarequest.com에 설명된 기준 및 프로세스에 따릅니다.

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