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En fas 2-studie av CPI-0610 med och utan ruxolitinib hos patienter med myelofibros

8 maj 2026 uppdaterad av: Constellation Pharmaceuticals

En fas 1/2-studie av CPI-0610, en liten molekylhämmare av BET-proteiner: Fas 1 (dosupptrappning av CPI-0610 hos patienter med hematologiska maligniteter) och Fas 2 (dosexpansion av CPI-0610 med och utan ruxolitinib hos patienter Med myelofibros och essentiell trombocytopeni)

Fas 1 del (komplett): Öppen, sekventiell dosökningsstudie av pelabresib hos patienter med tidigare behandlad akut leukemi, myelodysplastiskt syndrom, myelodysplastiska/myeloproliferativa neoplasmer och myelofibros.

Fas 2 Del: Öppen studie av CPI-0610 med och utan Ruxolitinib hos patienter med myelofibros.

CPI-0610 är en liten molekylhämmare av bromodomän och extraterminala (BET) proteiner.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

336

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Beskrivning

Inklusionskriterier:

Fas 2 del: Patienter med bekräftad diagnos av MF som uppfyller alla följande kriterier:

  • ANC ≥ 1 x 10^9/L utan hjälp av granulocyttillväxtfaktorer
  • Antal perifera blodsprängningar
  • ECOG-prestandastatus ≤ 2.
  • Adekvata hematologiska, njur-, lever- och koagulationslaboratoriebedömningar
  • Ingen tidigare behandling med BET-hämmare
  • Patienter måste ge skriftligt informerat samtycke för att delta i denna studie innan någon studierelaterad procedur utförs.

För arm 1 och 2 bör följande kriterier beaktas:

  • Patienter med bekräftad diagnos av MF som uppfyller alla följande kriterier
  • Dynamic International Prognostic Scoring System (DIPSS) riskkategori av mellan-2 eller högre
  • Mjältvolym ≥ 450 cm^3 med MRT eller CT för kohorter 1B och 2B ELLER RBC-transfusionsberoende (definierad som ett genomsnitt av ≥2 enheter RBC-transfusioner per månad (totalt mer än 6 RBC-transfusioner) under de 12 veckorna före inskrivning för kohorter 1A och 2A)
  • Minst 2 symtom kan mätas (poäng ≥ 1) med användning av Myelofibrosis Symptom Assessment Form Version 4.0 (MFSAF v4.0)
  • Trombocytantal ≥ 75 x 10^9/L utan hjälp av trombopoetiska faktorer eller transfusioner i minst 14 dagar
  • Arm (arm 1): Tidigare behandlad med en JAK-hämmare och vara intolerant, resistent, refraktär eller förlorad respons på JAK-hämmaren; inte har fått JAK-hämmaren inom 2 veckor före start av studieläkemedlet, eller är inte berättigade att behandlas med en JAK-hämmare
  • Kombinationsarm (arm 2): Måste ha fått ruxolitinib engångsmedel och vara på en stabil dos i minst 8 veckor men ha sjukdom som inte kontrolleras tillräckligt av ruxolitinib

För arm 3 (JAK-hämmare naiva) bör följande kriterier beaktas:

  • Patienter med bekräftad diagnos av MF som uppfyller alla följande kriterier
  • Dynamic International Prognostic Scoring System (DIPSS) riskkategori av mellan-2 eller högre
  • Trombocytantal ≥ 100 x 10^9/L utan hjälp av trombopoetiska faktorer eller transfusioner
  • Mjältvolym ≥ 450 cm^3 med MRT/CT
  • Minst 2 symtom kan mätas (poäng ≥ 3) eller en total poäng på ≥ 10 med användning av Myelofibrosis Symptom Assessment Form Version 4.0 (MFSAF v4.0)
  • Ingen tidigare behandling med JAKi tillåts

För arm 4 (ET Expansion) bör följande kriterier beaktas:

  • Patienter med en bekräftad diagnos av ET
  • Högrisksjukdom, definierad som att den uppfyller minst ett av följande kriterier:
  • Ålder > 60 år
  • Trombocytantal > 1500 × 10^9/L (när som helst under patientens sjukdom)
  • Tidigare dokumenterad trombos, erytromelalgi eller migrän
  • Tidigare blödning relaterad till ET
  • Diabetes eller hypertoni som kräver farmakologisk behandling i > 6 månader

  • Har ≥2 symtom med en genomsnittlig poäng ≥ 3 under 7-dagarsperioden före cykel 1 dag 1 eller en genomsnittlig totalpoäng på ≥15 under 7-dagarsperioden före cykel 1 dag 1 med hjälp av MPN ​​SAF

    • Blodplättar > 600 × 10^9/L
    • Resistent eller intolerant mot HU

Exklusions kriterier:

  • Aktuell känd aktiv eller kronisk infektion med humant immunbristvirus (HIV), Hepatit B eller Hepatit C.
  • Nedsatt hjärtfunktion eller kliniskt signifikanta hjärtsjukdomar
  • Patienter med Child-Pugh klass B eller C
  • Nedsättning av gastrointestinal (GI) funktion eller GI-sjukdom som signifikant kan förändra absorptionen av pelabresib och/eller ruxolitinib, inklusive eventuellt olöst illamående, kräkningar eller diarré som är CTCAE-grad >1
  • Tidigare behandling med BET-hämmare.
  • Gravida eller ammande kvinnor
  • Alla andra samtidiga allvarliga och/eller okontrollerade samtidiga medicinska tillstånd som kan äventyra deltagandet i studien
  • Patienter som inte vill eller kan följa detta studieprotokoll.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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).
Läkemedel: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Andra namn:
  • CPI-0610
  • DAK539
Experimentell: 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).
Läkemedel: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Andra namn:
  • CPI-0610
  • DAK539
Experimentell: 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).
Läkemedel: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Andra namn:
  • CPI-0610
  • DAK539
Läkemedel: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimentell: 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).
Läkemedel: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Andra namn:
  • CPI-0610
  • DAK539
Läkemedel: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimentell: 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).
Läkemedel: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Andra namn:
  • CPI-0610
  • DAK539

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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)

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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)
Tidsram: 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)
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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.

Andra resultatmått

Resultatmått
Tidsram
Fas 2 (Arm 1, 2 och 3): Utvärdera svarskategorifrekvens
Tidsram: Svarsfrekvens från den internationella arbetsgruppen - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) kriterier efter 24 veckor
Svarsfrekvens från den internationella arbetsgruppen - Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) kriterier efter 24 veckor
Fas 2 (armarna 1, 2 och 3): Utvärdera hastigheten för RBC-transfusion och RBC-transfusionsberoendehastigheten
Tidsram: Genomsnittligt antal RBC-enheter per ämnesmånad, upp till 24 veckor och längre
Genomsnittligt antal RBC-enheter per ämnesmånad, upp till 24 veckor och längre

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Constellation Pharmaceuticals

Samarbetspartners

The Leukemia and Lymphoma Society

Utredare

  • Studierektor: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

16 juli 2014

Primärt slutförande (Faktisk)

9 januari 2025

Avslutad studie (Faktisk)

9 januari 2025

Studieregistreringsdatum

Först inskickad

5 juni 2014

Först inskickad som uppfyllde QC-kriterierna

5 juni 2014

Första postat (Beräknad)

9 juni 2014

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

4 juni 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

8 maj 2026

Senast verifierad

1 april 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • 0610-02
  • 2018-000579-34 (EudraCT-nummer)
  • CDAK539A12201 (Annan identifierare: Novartis)

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

Novartis har åtagit sig att dela med kvalificerade externa forskare, tillgång till data på patientnivå och stödja kliniska dokument från berättigade studier. Dessa förfrågningar granskas och godkänns av en oberoende granskningspanel på grundval av vetenskaplig merit. All information som tillhandahålls är anonymiserad för att respektera integriteten för patienter som har deltagit i rättegången i enlighet med tillämpliga lagar och förordningar.

Denna tillgång till datumat är enligt kriterierna och processen som beskrivs på www.clinicalStudyDatareQuest.com

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Prenumerera