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Un estudio de TP-3654 oral en pacientes con mielofibrosis

30 de septiembre de 2026 actualizado por: Sumitomo Pharma America, Inc.

Un estudio de fase 1/2, abierto, de escalada de dosis, de seguridad, farmacocinético y farmacodinámico de TP-3654 oral en pacientes con mielofibrosis primaria o secundaria de riesgo intermedio o alto

This study is a Phase 1/2, multicenter, dose-escalation, open-label trial to assess safety, tolerability, pharmacokinetics and pharmacodynamics of nuvisertib (TP-3654) in patients with intermediate or high-risk primary or secondary MF.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

Arm 1 will enroll patients who have been previously treated and failed on a JAK inhibitor or ineligible to receive treatment with a JAK inhibitor.

Arm 2 will enroll patients who are on a stable dose of ruxolitinib, but who have either lost response or had a suboptimal or plateau in response.

Arm 3 will enroll patients who have been previously treated with a JAK inhibitor (except momelotinib)

Tipo de estudio

Intervencionista

Inscripción (Estimado)

240

Fase

  • Fase 2
  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Copia de seguridad de contactos de estudio

Ubicaciones de estudio

  • Alemania
      • Halle, Alemania
        • Reclutamiento
        • Universitätsmedizin Halle
        • Contacto:
          • SMPA Investigative Site
      • Lübeck, Alemania
        • Reclutamiento
        • Universitätsklinikum Schleswig-Holstein
        • Contacto:
          • SMPA Investigative Site
  • Australia
      • Adelaide, Australia
        • Reclutamiento
        • Icon Cancer Centre (Ashford Cancer Centre Research)
        • Contacto:
    • South Australia
      • Adelaide, South Australia, Australia
    • Victoria
      • Box Hill, Victoria, Australia
        • Reclutamiento
        • Eastern Health Box Hill Hospital
        • Contacto:
          • SMPA Investigative Site
      • Clayton, Victoria, Australia
        • Reclutamiento
        • Monash University
        • Contacto:
          • SMPA Investigative Site
      • Fitzroy, Victoria, Australia
        • Reclutamiento
        • St Vincent's Hospital Melbourne
        • Contacto:
          • SMPA Investigative Site
      • Melbourne, Victoria, Australia
        • Reclutamiento
        • Peter McCallum Center
        • Contacto:
          • SMPA Investigative Site
      • Richmond, Victoria, Australia
        • Reclutamiento
        • Epworth Healthcare
        • Contacto:
          • SMPA Investigative Site
  • Bélgica
      • Antwerp, Bélgica, 2020
        • Reclutamiento
        • ZNA Cadix
        • Contacto:
          • SMPA Investigative Site
      • Antwerp, Bélgica, 2030
        • Reclutamiento
        • ZNA Middelheim
        • Contacto:
          • SMPA Investigative Site
      • Ghent, Bélgica, 9000
        • Reclutamiento
        • Universitair Ziekenhuis Gent
        • Contacto:
          • SMPA Investigative Site
      • Liège, Bélgica, 4000
        • Reclutamiento
        • CHU de Liege
        • Contacto:
          • SMPA Investigative Site
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Bélgica, 3000
        • Reclutamiento
        • University Hospitals Leuven
        • Contacto:
          • SMPA Investigative Site
  • Canadá
    • Alberta
    • British Columbia
      • Vancouver, British Columbia, Canadá, V6T 1Z3
        • Reclutamiento
        • University of British Columbia
        • Contacto:
          • SMPA Investigative Site
      • Vancouver, British Columbia, Canadá, V6T 1Z3
        • Reclutamiento
        • St. Paul's Hospital Hematology/Oncology Research
        • Contacto:
    • Ontario
      • Hamilton, Ontario, Canadá, L8V 5C2
        • Reclutamiento
        • Juravinski Cancer Center
        • Contacto:
          • SMPA Investigative Site
      • Toronto, Ontario, Canadá, M5G 2M9
        • Reclutamiento
        • Princess Margaret Cancer Center
        • Contacto:
    • Quebec
      • Montreal, Quebec, Canadá, H3T 1E2
        • Reclutamiento
        • Jewish General Hospital
        • Contacto:
          • SMPA Investigative Site
  • España
      • Barcelona, España
        • Reclutamiento
        • Hospital Universitario y Politecnico La Fe
        • Contacto:
          • SMPA Investigative Site
      • Barcelona, España
        • Reclutamiento
        • Institut Catala d'Oncologia
        • Contacto:
          • SMPA Investigative Site
      • Salamanca, España
        • Reclutamiento
        • Hospital Universitario de Salamanca
        • Contacto:
          • SMPA Investigative Site
  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos, 35294
        • Reclutamiento
        • University of Alabama
        • Contacto:
          • Tiffany Hill
          • Número de teléfono: 205-934-9591
    • Arizona
      • Tucson, Arizona, Estados Unidos, 85724
        • Reclutamiento
        • The University of Arizona Cancer Center
        • Contacto:
    • California
      • Duarte, California, Estados Unidos, 91010
        • Reclutamiento
        • City of Hope
        • Contacto:
          • Michelle Velasquez
          • Número de teléfono: 626-218-3524
          • Correo electrónico: mvelaszuez@coh.org
      • Los Angeles, California, Estados Unidos, 90033
        • Reclutamiento
        • University of Southern California
        • Contacto:
      • Newport Beach, California, Estados Unidos, 92663
        • Reclutamiento
        • Hoag Family Cancer Institute
        • Contacto:
    • Colorado
      • Denver, Colorado, Estados Unidos, 80218
    • Connecticut
      • New Haven, Connecticut, Estados Unidos, 06510
        • Reclutamiento
        • Yale School of Medicine
        • Contacto:
    • Florida
      • Gainesville, Florida, Estados Unidos, 32608
        • Terminado
        • University of Florida Health Shands Cancer Hospital
      • Miami, Florida, Estados Unidos, 33136
        • Reclutamiento
        • University of Miami
        • Contacto:
          • Alessia Zoso
          • Número de teléfono: 305-243-0327
          • Correo electrónico: azoso@miami.edu
      • Miami, Florida, Estados Unidos, 33176
        • Reclutamiento
        • Baptist Health - Miami Cancer Institute
        • Contacto:
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Reclutamiento
        • Emory University
        • Contacto:
    • Illinois
      • Chicago, Illinois, Estados Unidos, 60637
    • Maryland
      • Baltimore, Maryland, Estados Unidos, 21201
        • Reclutamiento
        • University of Maryland
        • Contacto:
          • Maria Baer, MD
          • Número de teléfono: 410-328-8708
          • Correo electrónico: mbaer@umm.edu
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02114
        • Reclutamiento
        • Massachusetts General Hospital
        • Contacto:
    • Michigan
      • Ann Arbor, Michigan, Estados Unidos, 48109
        • Reclutamiento
        • University of Michigan
        • Contacto:
    • Minnesota
      • Minneapolis, Minnesota, Estados Unidos, 55455
        • Reclutamiento
        • University of Minnesota
        • Contacto:
    • Missouri
      • St Louis, Missouri, Estados Unidos, 63110
        • Reclutamiento
        • Washington University of Medicine
        • Contacto:
          • Nicole Gaudin
          • Número de teléfono: 314-747-7960
          • Correo electrónico: nrgaudin@wustl.edu
    • New Jersey
      • Hackensack, New Jersey, Estados Unidos, 07601
        • Reclutamiento
        • John Theurer Cancer Center at Hackensack University Medical Center
        • Contacto:
    • New York
      • Buffalo, New York, Estados Unidos, 14263
        • Terminado
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, Estados Unidos, 10065
        • Reclutamiento
        • Memorial Sloan Kettering Cancer Center
        • Contacto:
      • New York, New York, Estados Unidos, 10029
        • Reclutamiento
        • Icahn School of Medicine at Mount Sinai
        • Contacto:
      • New York, New York, Estados Unidos, 10065
        • Reclutamiento
        • Weill Cornell Medical Center
        • Contacto:
      • The Bronx, New York, Estados Unidos, 10461
    • North Carolina
      • Durham, North Carolina, Estados Unidos, 27710
    • Ohio
      • Columbus, Ohio, Estados Unidos, 43210
        • Reclutamiento
        • Ohio State University
        • Contacto:
    • South Carolina
      • Charleston, South Carolina, Estados Unidos, 29425
        • Reclutamiento
        • Medical University of South Carolina
        • Contacto:
    • Tennessee
      • Nashville, Tennessee, Estados Unidos, 37232
        • Reclutamiento
        • Vanderbilt University
        • Contacto:
          • SMPA Investigative Site
      • Nashville, Tennessee, Estados Unidos, 37203
    • Texas
      • Houston, Texas, Estados Unidos, 77054
        • Reclutamiento
        • MD Anderson Cancer Center
        • Contacto:
    • Utah
      • Salt Lake City, Utah, Estados Unidos, 84112
        • Reclutamiento
        • Huntsman Cancer Institute
        • Contacto:
    • Virginia
      • Charlottesville, Virginia, Estados Unidos, 22903
        • Reclutamiento
        • University of Virginia Cancer Center
        • Contacto:
    • Washington
      • Seattle, Washington, Estados Unidos, 98109
        • Reclutamiento
        • University of Washington - Fred Hutchinson Cancer Center
        • Contacto:
  • Francia
      • Amiens, Francia, 80054
        • Reclutamiento
        • Centre Hospitalier Universitaire D'Amiens
        • Contacto:
          • SMPA Investigative Site
      • Angers, Francia, 9000
        • Reclutamiento
        • CHU Angers
        • Contacto:
          • SMPA Investigative Site
      • Lyon, Francia, 69495
        • Reclutamiento
        • Centre Hospitalier Lyon Sud
        • Contacto:
          • SMPA Investigative Site
      • Nice, Francia, 06200
        • Reclutamiento
        • Hospitalier Universitaire (CHU) de Nice - Hopital de l'Archet
        • Contacto:
          • SMPA Investigative Site
      • Nîmes, Francia, 30029
        • Reclutamiento
        • Institut de cancerologie du Gard
        • Contacto:
          • SMPA Investigative Site
      • Nîmes, Francia
        • Reclutamiento
        • Institut de cancerologie du Gard
        • Contacto:
          • SMPA Investigative Site
      • Paris, Francia, 75010
        • Reclutamiento
        • Hospital Saint Louis
        • Contacto:
          • SMPA Investigative Site
      • Poitiers, Francia, 86021
        • Reclutamiento
        • University Hospital of Poitiers
        • Contacto:
          • SMPA Investigative Site
      • Villejuif, Francia, 94805
        • Reclutamiento
        • Institut Gustave Roussy
        • Contacto:
          • SMPA Investigative Site
  • Italia
      • Alessandria, Italia, 15121
        • Reclutamiento
        • Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare Arrigo
        • Contacto:
          • SMPA Investigative Site
      • Aviano, Italia, 33081
        • Reclutamiento
        • Istituto Nazionale Tumori, IRCCS Centro di Riferimento Oncologico di Aviano
      • Bologna, Italia, 40138
        • Reclutamiento
        • IRCCS Azienda Ospedaliero -Universitaria Di Bologna - Dipartimento Malattie Oncologiche ed Ematologiche - UO Ematologia
        • Contacto:
          • SMPA Investigative Site
      • Brescia, Italia
        • Reclutamiento
        • ASST - Spedali Civili di Brescia
        • Contacto:
          • SMPA Investigative Site
      • Meldola, Italia, 47014
        • Reclutamiento
        • IRCCS istituto Romagnolo per lo studio dei tumori "Dino Amadori"
        • Contacto:
          • SMPA Investigative Site
      • Milan, Italia, 20122
        • Reclutamiento
        • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
        • Contacto:
          • SMPA Investigative Site
      • Torino, Italia, 10126
        • Reclutamiento
        • Azienda Ospedaliera Universitaria Citta' Della Salute E della Scienza di Torino
        • Contacto:
          • SMPA Investigative Site
  • Japón
      • Aichi, Japón
      • Aomori, Japón
        • Reclutamiento
        • Aomori Prefectural Central Hospital
        • Contacto:
      • Chiba, Japón
        • Reclutamiento
        • National Cancer Center Hospital East
        • Contacto:
      • Fukuoka, Japón
      • Hokkaido, Japón
        • Reclutamiento
        • Hokkaido University Hospital
        • Contacto:
      • Kamakura, Japón, 247-8533
        • Reclutamiento
        • Shonan Kamakura General Hospital
        • Contacto:
      • Miyazaki, Japón
        • Reclutamiento
        • University of Miyazaki Hospital
        • Contacto:
      • Okayama, Japón
        • Reclutamiento
        • Okayama University Hospital
        • Contacto:
      • Osaka, Japón
        • Reclutamiento
        • The University of Osaka Hospital
        • Contacto:
          • Michiko Ichii, MD
          • Número de teléfono: 06-6879-5111
      • Saitama, Japón
        • Terminado
        • Saitama Medical Center
      • Sendai, Japón
        • Reclutamiento
        • Tohoku University Hospital
        • Contacto:
          • Noriko Fukuhara, MD
          • Número de teléfono: 022-717-7000
      • Shizuoka, Japón
        • Terminado
        • Shizuoka Cancer Center
      • Tokyo, Japón, 160-0023
        • Reclutamiento
        • Tokyo Medical University Hospital
        • Contacto:
      • Tokyo, Japón
        • Reclutamiento
        • Juntendo University Hospital
        • Contacto:
      • Tokyo, Japón, 179-0072
        • Reclutamiento
        • Nerima Hikarigaoka Hospital
        • Contacto:
      • Tsu, Japón
        • Reclutamiento
        • Mie University Hospital
        • Contacto:
  • Reino Unido
      • Lincoln, Reino Unido
        • Reclutamiento
        • Lincoln County Hospital
        • Contacto:
          • SMPA Investigative Site
      • Lincoln, Reino Unido
        • Reclutamiento
        • United Lincolnshire Hospitals NHS Trust - Pilgrim Hospital
        • Contacto:
          • SMPA Investigative Site
      • London, Reino Unido
        • Reclutamiento
        • University College London Hospital's NHS foundation Trust
        • Contacto:
          • SMPA Investigative Site
      • Oxford, Reino Unido
        • Reclutamiento
        • Oxford University Hospitals NHS Foundation
        • Contacto:
          • SMPA Investigative Site

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Patients must meet all of the following inclusion criteria to be eligible:

Nuvisertib (TP-3654) Monotherapy Arm:

  • Confirmed pathological diagnosis of primary myelofibrosis (PMF) or post-PV-MF/post-ET- MF and intermediate or high-risk primary or secondary MF
  • Previously treated with JAK inhibitor(s) and is intolerant, resistant, refractory or has lost response to the JAK inhibitor(s) or is ineligible to be treated with JAK inhibitor
  • Fulfill the following clinical laboratory parameters:
  • Platelet count ≥ 25 x 10^9 /L, without assistance of growth factors or platelet transfusions
  • ANC ≥ 1 x 10^9/L without assistance of granulocyte growth factors
  • Peripheral blood blast count < 5%
  • ECOG performance status ≤ 1
  • Life expectancy ≥ 6 months
  • Adequate renal function
  • Adequate hepatic function
  • Adequate coagulation function
  • Splenomegaly (spleen volume of ≥ 450 cm3 by MRI or CT scan) within 2 weeks prior to Cycle 1 Day 1.
  • Dose escalation: At least 2 symptoms measurable (score ≥ 1) using the MF-SAF
  • Dose expansion: At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF

Nuvisertib (TP-3654) + Ruxolitinib Arm:

  • Confirmed pathological diagnosis of PMF or post-PV-MF/post ET- MF and intermediate or high-risk primary or secondary MF
  • On ruxolitinib treatment for ≥ 6 months, and on a stable dose of ruxolitinib (5 to 25 mg BID) for ≥ 8 weeks prior to the first dose of nuvisertib, but has either lost response or had a suboptimal or plateau in response
  • Fulfills the following clinical laboratory parameters:
  • Platelet count ≥ 50 × 10^9/L (without assistance of growth factors or platelet transfusions)
  • ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
  • Peripheral blood blast count < 5% at screening
  • Adequate renal function
  • Adequate hepatic function
  • Adequate coagulation function
  • Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
  • At least 2 symptoms measurable with each score ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
  • ECOG performance status ≤ 1
  • Life expectancy ≥ 6 months

Nuvisertib (TP-3654) + Momelotinib Arm

  • Confirmed pathological diagnosis of PMF or post-PV-MF/post ET-MF and intermediate or high-risk primary or secondary MF
  • Previously treated with an approved JAK inhibitor (except momelotinib) for PMF or Post-PV/ET MF for ≥ 12 weeks, or ≥ 4 weeks if JAK inhibitor therapy was complicated by a transfusion requirement of ≥ 4 units of red blood cells in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma
  • Fulfills the following clinical laboratory parameters:
  • Anemic, defined as Hb <10 g/dL or requiring RBC transfusion at baseline
  • Platelet count ≥ 50 × 109/L (without assistance of growth factors or platelet transfusions)
  • ANC ≥ 1 × 109/L without assistance of granulocyte growth factors
  • Peripheral blood blast count < 5% at screening
  • Adequate renal function
  • Adequate hepatic function
  • Adequate coagulation function
  • Splenomegaly (spleen volume of ≥ 450 cm3 by MRI/CT scan) within 2 weeks prior to Cycle 1 Day 1
  • At least 2 symptoms measurable with each score of ≥ 3 or a total average score of ≥ 10 per MFSAF v4.0
  • ECOG performance status ≤ 1
  • Life expectancy ≥ 6 months

Patients meeting any one of these exclusion criteria will be prohibited from participating in this study:

Nuvisertib (TP-3654) Monotherapy Arm:

  • Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1. Hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
  • Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or not recovered adequately from from surgery prior to first dose.
  • Splenic irradiation within 6 months prior to Screening or prior splenectomy.
  • Prior allogeneic stem cell transplant within the last 6 months.
  • Eligible for allogeneic bone marrow or stem cell transplantation.
  • Unresolved Grade ≥ 2 non-hematological toxicity related to prior treatment
  • History of symptomatic congestive heart failure, or myocardial infarction, or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; left ventricular ejection fraction (LVEF) < 45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1.
  • Corrected QT interval > 480msec.
  • Prior or concurrent malignancy that could interfere with the investigational regime.
  • Known history of chronic liver disease, e.g. portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic antimicrobial within 1 week prior to Cycle 1 Day 1.
  • Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
  • Exhibited allergic reactions or sensitivity to nuvisertib, or similar compound.
  • Medical condition or GI tract surgery that could impair absorption or result in short bowel syndrome with diarrhea.
  • Systemic steroid therapy (>10 mg daily prednisone or equivalent) within 1 week prior to the first dose of study treatment (note: topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding.
  • Pregnant or breastfeeding
  • Currently receiving any other investigational agent.

Nuvisertib (TP-3654) + Ruxolitinib Arm:

  • Received previous systemic antineoplastic therapy (other than ruxolitinib) or any other experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Note: Prior treatment with nuvisertib is not allowed. Hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
  • Received systemic steroid therapy (>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited)
  • Known allergic reactions or sensitivity to nuvisertib, or similar compound.
  • Splenic irradiation within 6 months prior to Screening or prior splenectomy
  • Prior allogeneic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
  • Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible.)
  • Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately prior to first dose.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
  • Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
  • Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver morphology at baseline imaging may require additional testing, as needed).
  • Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
  • History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF <45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
  • Corrected QTcF of > 480 msec
  • Prior or concurrent malignancy that could interfere with the safety or efficacy assessment of the study intervention
  • History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
  • Pregnant or breastfeeding

Nuvisertib (TP-3654) + Momelotinib Arm:

  • Received previous systemic antineoplastic therapy or any experimental therapy within 2 weeks or 5 half-lives, whichever is longer, prior to Cycle 1 Day 1 (Notes: Prior treatment with momelotinib or nuvisertib is not allowed; in patients with ongoing JAK inhibitor therapy, ie, ruxolitinib, at screening, JAK inhibitor therapy must be tapered over a period of at least 1 week. Patients on a low dose of ruxolitinib (eg, 5 mg QD) may have a reduced taper period or no taper; hydroxyurea or anagrelide are allowed up to 24 hours prior to Cycle 1 Day 1).
  • Received systemic steroid therapy (>10 mg daily prednisone or equivalent) within 1 week prior to Cycle 1 Day 1 (Note: Topical, inhaled, nasal, and ophthalmic steroids are not prohibited).
  • Known allergic reactions or sensitivity to nuvisertib, momelotinib, or any structurally similar drug, or to any component of the formulations of either study intervention
  • Splenic irradiation within 6 months prior to screening or prior splenectomy
  • Prior allogenic stem cell transplant within the last 6 months (Note: Patients who have relapsed after 6 months post-transplant and do not have active GVHD are eligible).
  • Eligible for allogeneic bone marrow or stem cell transplantation (Note: Patients who are not willing to undergo transplantation or for whom a suitable donor is not available are considered as transplant ineligible).
  • Major surgery within 4 weeks prior to Cycle 1 Day 1 and/or have not recovered adequately from surgery prior to first dose.
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring parenteral antimicrobial within 1 week prior to Cycle 1 Day 1
  • Chronic active or acute viral hepatitis A, B, or C infection (testing for hepatitis B and C are required)
  • Known history of chronic liver disease (eg, portal hypertension or any of its complications, cirrhosis, Child-Pugh C, auto-immune hepatitis, alpha-1 anti-trypsin deficiency, Wilson's disease, etc) (Note: Abnormal liver morphology at baseline imaging may require additional testing, as needed)
  • Unresolved Grade ≥ 2 non-hematological adverse events related to prior treatment (stable Grade 2 conditions may be permitted in consultation with the Sponsor)
  • Presence of Grade ≥ 2 peripheral neuropathy
  • History of myocardial infarction or symptomatic congestive heart failure or uncontrolled arrhythmia within 6 months prior to Cycle 1 Day 1; LVEF < 45% by echocardiogram within 4 weeks prior to Cycle 1 Day 1
  • Corrected QTcF of > 480 msec
  • Prior or concurrent malignancy that could interfere with the safety or efficacy assessment of the study intervention
  • History of a medical condition or GI tract surgery that could impair absorption or could result in short bowel syndrome with diarrhea
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or thalassemia, or severe GI bleeding
  • Pregnant or breastfeeding

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: No aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Grupo 1: nuvisertib (TP-3654)
Droga: Nusivertib

Oral PIM Inhibitor

Otros nombres:
  • TP-3654
Experimental: Grupo 2: nuvisertib (TP-3654) añadido a ruxolitinib
Droga: Nusivertib

Oral PIM Inhibitor

Otros nombres:
  • TP-3654
Droga: Ruxolitinib

Oral JAK inhibitor

Otros nombres:
  • Yakafi
Experimental: Grupo 3: nuvisertib (TP-3654) en combinación con momelotinib
Droga: Nusivertib

Oral PIM Inhibitor

Otros nombres:
  • TP-3654
Droga: Momelotinib

Oral JAK inhibitor

Otros nombres:
  • Ojjaara

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Determine the incidence of dose-limiting toxicities (DLTs)
Periodo de tiempo: 28 days

Number of participants with DLTs
28 days
Determine the incidence of treatment emergent adverse events
Periodo de tiempo: From start of treatment to end of study

Number of participants with Treatment Emergent Adverse Events and Serious Adverse Events
From start of treatment to end of study
Assess patients for any evidence of preliminary activity by determining the number of patients with ≥ 35% spleen volume reduction (SVR35)
Periodo de tiempo: From start of treatment to end of study

Number of participants with ≥ 35% spleen volume reduction (SVR35)
From start of treatment to end of study

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of participants achieving objective response by IWG-MRT response criteria
Periodo de tiempo: From start of treatment to end of study

Number of participants achieving complete remission, partial remission, clinical improvement, progressive disease and stable disease.
From start of treatment to end of study
Number of participants who have ≥ 25% spleen volume reduction
Periodo de tiempo: Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment.

Number of participants who have ≥ 25% spleen volume reduction compared to baseline
Every 12 weeks from cycle 1 day 1 through cycle 19 day 1, and then every 24 weeks therafter during treatment.
Number of participants with ≥ 50% improvement in total symptom score (TSS50) at week 24
Periodo de tiempo: 24 weeks

Number of participants who have ≥ 50% total symptom score reduction by MFSAF compared to baseline after 24 weeks of treatment.
24 weeks
Determine the change in Patient Global Impression of Change (PGIC) at week 24 through end of study.
Periodo de tiempo: After 24 weeks of treatment to end of study

Change in PGIC score
After 24 weeks of treatment to end of study
Determine the incidence of QT interval changes
Periodo de tiempo: 25 hours

Changes in QT interval and heart rhythm
25 hours
Establish the half-life (t½) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib
Periodo de tiempo: 24 hours

The estimate of time for the nuvisertib concentration or amount to be reduced by half
24 hours
Establish the Area under the plasma concentration versus time curve (AUC) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib
Periodo de tiempo: 24 hours

The amount of drug exposure over 24 hours period after administration
24 hours
Establish the Peak Plasma Concentration (Cmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib
Periodo de tiempo: 24 hours

The maximum nuvisertib concentration after administration
24 hours
Establish the Time of Maximum concentration observed (tmax) of nuvisertib monotherapy, in combination with ruxolitinib, and in combination with momelotinib
Periodo de tiempo: 24 hours

The time to reach maximum nuvisertib concentration
24 hours

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
Número de pacientes con reducción de la fibrosis de la médula ósea
Periodo de tiempo: Cada 24 semanas hasta el final del estudio.
Cada 24 semanas hasta el final del estudio.
Brazos combinados de nuvisertib: evaluar el aumento de hemoglobina ≥1,5 o ≥ 2 g/dl desde el inicio
Periodo de tiempo: Desde el inicio del tratamiento hasta el final del estudio.
Desde el inicio del tratamiento hasta el final del estudio.
Brazos combinados de nuvisertib: evaluar el estado de independencia de la transfusión de glóbulos rojos o cualquier cambio en los requisitos
Periodo de tiempo: Desde el inicio del tratamiento hasta el final del estudio.
Desde el inicio del tratamiento hasta el final del estudio.
Monoterapia de nuvisertib: cambios en el recuento de plaquetas con el tiempo en pacientes con recuento de plaquetas basal <100 x 10^9/L
Periodo de tiempo: Desde el inicio del tratamiento hasta el final del estudio
Desde el inicio del tratamiento hasta el final del estudio
Study potential pharmacodynamic (PD) markers of nuvisertib
Periodo de tiempo: 12 months

Evaluate exploratory biomarkers, including change in protein phosphorylation and inflammatory cytokines, in peripheral blood samples and bone marrow biopsy samples.
12 months
Establish overall survival
Periodo de tiempo: From start of treatment to end of study

The time interval from treatment start date to date of death from any cause
From start of treatment to end of study

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Sumitomo Pharma America, Inc.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

16 de diciembre de 2019

Finalización primaria (Estimado)

30 de abril de 2027

Finalización del estudio (Estimado)

30 de abril de 2030

Fechas de registro del estudio

Enviado por primera vez

8 de noviembre de 2019

Primero enviado que cumplió con los criterios de control de calidad

22 de noviembre de 2019

Publicado por primera vez (Actual)

25 de noviembre de 2019

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de octubre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

30 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • BBI-TP-3654-102

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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