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Um estudo de fase 2 de CPI-0610 com e sem Ruxolitinibe em pacientes com mielofibrose

8 de maio de 2026 atualizado por: Constellation Pharmaceuticals

Um Estudo de Fase 1/2 de CPI-0610, um Inibidor de Pequena Molécula de Proteínas BET: Fase 1 (Escalonamento de Dose de CPI-0610 em Pacientes com Malignidades Hematológicas) e Fase 2 (Expansão de Dose de CPI-0610 Com e Sem Ruxolitinib em Pacientes Com Mielofibrose e Trombocitopenia Essencial)

Fase 1 Parte (completa): Estudo aberto, escalonamento de dose sequencial de pelabresibe em pacientes com leucemia aguda tratada anteriormente, síndrome mielodisplásica, neoplasias mielodisplásicas/mieloproliferativas e mielofibrose.

Fase 2 Parte: Estudo aberto de CPI-0610 com e sem Ruxolitinibe em pacientes com Mielofibrose.

O CPI-0610 é um inibidor de moléculas pequenas de bromodomínio e proteínas extra-terminais (BET).

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Tipo de estudo

Intervencional

Inscrição (Real)

336

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Descrição

Critério de inclusão:

Fase 2 parte: Pacientes com diagnóstico confirmado de MF que atendem a todos os seguintes critérios:

  • ANC ≥ 1 x 10^9/L sem a ajuda de fatores de crescimento de granulócitos
  • Contagem de explosão de sangue periférico
  • Estado de desempenho ECOG ≤ 2.
  • Adequadas avaliações laboratoriais hematológicas, renais, hepáticas e de coagulação
  • Nenhum tratamento anterior com um inibidor BET
  • Os pacientes devem dar consentimento informado por escrito para participar deste estudo antes da realização de qualquer procedimento relacionado ao estudo.

Para os Braços 1 e 2, os seguintes critérios devem ser considerados:

  • Pacientes com diagnóstico confirmado de MF que preenchem todos os seguintes critérios
  • Categoria de risco do Sistema Internacional de Pontuação de Prognóstico Dinâmico (DIPSS) intermediário-2 ou superior
  • Volume do baço ≥ 450 cm^3 por ressonância magnética ou tomografia computadorizada para Coortes 1B e 2B OU dependente de transfusão de hemácias (definido como uma média de ≥2 unidades de transfusões de hemácias por mês (total superior a 6 transfusões de hemácias) nas 12 semanas anteriores à inscrição para Coortes 1A e 2A)
  • Pelo menos 2 sintomas mensuráveis ​​(Pontuação ≥ 1) usando o Formulário de Avaliação de Sintomas de Mielofibrose Versão 4.0 (MFSAF v4.0)
  • Contagem de plaquetas ≥ 75 x 10^9/L sem auxílio de fatores trombopoiéticos ou transfusões por pelo menos 14 dias
  • Braço (Braço 1): previamente tratado com um inibidor de JAK e ser intolerante, resistente, refratário ou perdeu a resposta ao inibidor de JAK; não receberam o inibidor de JAK dentro de 2 semanas antes do início do medicamento do estudo ou não são elegíveis para serem tratados com um inibidor de JAK
  • Braço de combinação (Braço 2): Deve ter recebido ruxolitinibe como agente único e estar em uma dose estável por no mínimo 8 semanas, mas ter doença que não está sendo adequadamente controlada por ruxolitinibe

Para o Braço 3 (virgem de inibidores de JAK), os seguintes critérios devem ser considerados:

  • Pacientes com diagnóstico confirmado de MF que preenchem todos os seguintes critérios
  • Categoria de risco do Sistema Internacional de Pontuação de Prognóstico Dinâmico (DIPSS) intermediário-2 ou superior
  • Contagem de plaquetas ≥ 100 x 10^9/L sem auxílio de fatores trombopoiéticos ou transfusões
  • Volume do baço ≥ 450 cm^3 por ressonância magnética/TC
  • Pelo menos 2 sintomas mensuráveis ​​(Pontuação ≥ 3) ou uma pontuação total ≥ 10 usando o Formulário de Avaliação de Sintomas de Mielofibrose Versão 4.0 ( MFSAF v4.0)
  • Nenhum tratamento prévio com JAKi permitido

Para o Braço 4 (Expansão do ET) devem ser considerados os seguintes critérios:

  • Pacientes com diagnóstico confirmado de TE
  • Doença de alto risco, definida como preenchendo pelo menos um dos seguintes critérios:
  • Idade > 60 anos
  • Contagem de plaquetas > 1500 × 10^9/L (em qualquer momento durante a doença do paciente)
  • Trombose, eritromelalgia ou enxaqueca previamente documentadas
  • Hemorragia prévia relacionada a TE
  • Diabetes ou hipertensão requerendo terapia farmacológica por > 6 meses

  • Ter ≥2 sintomas com uma pontuação média ≥ 3 durante o período de 7 dias antes do Ciclo 1 Dia 1 ou uma pontuação total média de ≥15 durante o período de 7 dias antes do Ciclo 1 Dia 1 usando o MPN SAF

    • Plaquetas > 600 × 10^9/L
    • Resistente ou intolerante a HU

Critério de exclusão:

  • Infecção atual conhecida ativa ou crônica pelo vírus da imunodeficiência humana (HIV), Hepatite B ou Hepatite C.
  • Função cardíaca prejudicada ou doenças cardíacas clinicamente significativas
  • Pacientes com Child-Pugh Classe B ou C
  • Comprometimento da função gastrointestinal (GI) ou doença GI que pode alterar significativamente a absorção de pelabresibe e/ou ruxolitinibe, incluindo qualquer náusea, vômito ou diarreia não resolvida que seja de Grau CTCAE >1
  • Tratamento prévio com um inibidor de BET.
  • Mulheres grávidas ou lactantes
  • Qualquer outra condição médica concomitante grave e/ou não controlada que possa comprometer a participação no estudo
  • Pacientes que não desejam ou não podem cumprir este protocolo de estudo.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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).
Medicamento: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Outros nomes:
  • CPI-0610
  • DAK539
Experimental: 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).
Medicamento: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Outros nomes:
  • CPI-0610
  • DAK539
Experimental: 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).
Medicamento: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Outros nomes:
  • CPI-0610
  • DAK539
Medicamento: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimental: 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).
Medicamento: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Outros nomes:
  • CPI-0610
  • DAK539
Medicamento: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimental: 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).
Medicamento: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Outros nomes:
  • CPI-0610
  • DAK539

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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)

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.

Outras medidas de resultado

Medida de resultado
Prazo
Fase 2 (Braços 1, 2 e 3): Avalie a taxa de categoria de resposta
Prazo: Taxa de resposta pelos critérios do Grupo de Trabalho Internacional - Pesquisa e Tratamento de Neoplasias Mieloproliferativas (IWG-MRT) após 24 semanas
Taxa de resposta pelos critérios do Grupo de Trabalho Internacional - Pesquisa e Tratamento de Neoplasias Mieloproliferativas (IWG-MRT) após 24 semanas
Fase 2 (Braços 1, 2 e 3): Avaliar a taxa de transfusão de hemácias e a taxa de dependência de transfusão de hemácias
Prazo: Número médio de unidades de RBC por indivíduo-mês, até 24 semanas e além
Número médio de unidades de RBC por indivíduo-mês, até 24 semanas e além

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Constellation Pharmaceuticals

Colaboradores

The Leukemia and Lymphoma Society

Investigadores

  • Diretor de estudo: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

16 de julho de 2014

Conclusão Primária (Real)

9 de janeiro de 2025

Conclusão do estudo (Real)

9 de janeiro de 2025

Datas de inscrição no estudo

Enviado pela primeira vez

5 de junho de 2014

Enviado pela primeira vez que atendeu aos critérios de CQ

5 de junho de 2014

Primeira postagem (Estimado)

9 de junho de 2014

Atualizações de registro de estudo

Última Atualização Postada (Real)

4 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

8 de maio de 2026

Última verificação

1 de abril de 2026

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • 0610-02
  • 2018-000579-34 (Número EudraCT)
  • CDAK539A12201 (Outro identificador: Novartis)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

A Novartis está comprometida em compartilhar com pesquisadores externos qualificados o acesso a dados de pacientes e documentos clínicos de apoio de estudos elegíveis. Estas solicitações são analisadas e aprovadas por um painel de revisão independente com base no mérito científico. Todos os dados fornecidos são anonimizados para respeitar a privacidade dos pacientes que participaram do estudo, de acordo com as leis e regulamentos aplicáveis.

A disponibilidade dos dados deste ensaio está de acordo com os critérios e processos descritos em www.clinicalstudydatarequest.com

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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