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Een studie van orale TP-3654 bij patiënten met myelofibrose

30 september 2026 bijgewerkt door: Sumitomo Pharma America, Inc.

Een fase 1/2, open-label, dosis-escalatie, veiligheids-, farmacokinetische en farmacodynamische studie van orale TP-3654 bij patiënten met intermediair of hoog risico primaire of secundaire myelofibrose

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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)

Studietype

Ingrijpend

Inschrijving (Geschat)

240

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm 1: nuvisertib (TP-3654)
Geneesmiddel: Nusivertib

Oral PIM Inhibitor

Andere namen:
  • TP-3654
Experimenteel: Arm 2: nuvisertib (TP-3654) toegevoegd aan ruxolitinib
Geneesmiddel: Nusivertib

Oral PIM Inhibitor

Andere namen:
  • TP-3654
Geneesmiddel: Ruxolitinib

Oral JAK inhibitor

Andere namen:
  • Jakafi
Experimenteel: Arm 3: nuvisertib (TP-3654) in combinatie met momelotinib
Geneesmiddel: Nusivertib

Oral PIM Inhibitor

Andere namen:
  • TP-3654
Geneesmiddel: Momelotinib

Oral JAK inhibitor

Andere namen:
  • Ojjaara

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Determine the incidence of dose-limiting toxicities (DLTs)
Tijdsspanne: 28 days

Number of participants with DLTs
28 days
Determine the incidence of treatment emergent adverse events
Tijdsspanne: 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)
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of participants achieving objective response by IWG-MRT response criteria
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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.
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 24 hours

The time to reach maximum nuvisertib concentration
24 hours

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Aantal patiënten met vermindering van beenmergfibrose
Tijdsspanne: Elke 24 weken tot einde studie
Elke 24 weken tot einde studie
Nuvisertib-combinatiearmen: Beoordeel de stijging van hemoglobine ≥1,5 of ≥ 2 g/dl ten opzichte van de uitgangswaarde
Tijdsspanne: Van start behandeling tot einde studie
Van start behandeling tot einde studie
Nuvisertib-combinatiearmen: Beoordeel de onafhankelijkheidsstatus van rode bloedcellentransfusies of eventuele wijzigingen in de vereisten
Tijdsspanne: Van start behandeling tot einde studie
Van start behandeling tot einde studie
Nuvisertib monotherapie: veranderingen in het aantal bloedplaatjes in de loop van de tijd bij patiënten met baseline bloedplaatjes tellen <100 x 10^9/l
Tijdsspanne: Vanaf het begin van de behandeling tot het einde van de studie
Vanaf het begin van de behandeling tot het einde van de studie
Study potential pharmacodynamic (PD) markers of nuvisertib
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Sumitomo Pharma America, Inc.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

16 december 2019

Primaire voltooiing (Geschat)

30 april 2027

Studie voltooiing (Geschat)

30 april 2030

Studieregistratiedata

Eerst ingediend

8 november 2019

Eerst ingediend dat voldeed aan de QC-criteria

22 november 2019

Eerst geplaatst (Werkelijk)

25 november 2019

Updates van studierecords

Laatste update geplaatst (Werkelijk)

2 oktober 2026

Laatste update ingediend die voldeed aan QC-criteria

30 september 2026

Laatst geverifieerd

1 september 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • BBI-TP-3654-102

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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