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Studie fáze 2 CPI-0610 s ruxolitinibem a bez něj u pacientů s myelofibrózou

8. května 2026 aktualizováno: Constellation Pharmaceuticals

Studie fáze 1/2 CPI-0610, inhibitoru malé molekuly proteinů BET: fáze 1 (eskalace dávky CPI-0610 u pacientů s hematologickými malignitami) a fáze 2 (rozšíření dávky CPI-0610 s ruxolitinibem a bez něj u pacientů S myelofibrózou a esenciální trombocytopenií)

Část fáze 1 (kompletní): Otevřená studie se sekvenčním zvyšováním dávky pelabresibu u pacientů s dříve léčenou akutní leukémií, myelodysplastickým syndromem, myelodysplastickými/myeloproliferativními novotvary a myelofibrózou.

Část 2. fáze: Otevřená studie CPI-0610 s ruxolitinibem a bez něj u pacientů s myelofibrózou.

CPI-0610 je malomolekulární inhibitor bromodomény a extra-terminálních (BET) proteinů.

Přehled studie

Postavení

Dokončeno

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

336

Fáze

  • Fáze 2
  • Fáze 1

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

18 let a starší (Dospělý, Starší dospělý)

Přijímá zdravé dobrovolníky

Ne

Popis

Kritéria pro zařazení:

Část 2. fáze: Pacienti s potvrzenou diagnózou MF, kteří splňují všechna následující kritéria:

  • ANC ≥ 1 x 10^9/l bez asistence růstových faktorů granulocytů
  • Počet výbuchů v periferní krvi
  • Stav výkonu ECOG ≤ 2.
  • Adekvátní hematologická, renální, jaterní a koagulační laboratorní vyšetření
  • Žádná předchozí léčba inhibitorem BET
  • Pacienti musí dát písemný informovaný souhlas s účastí na této studii před provedením jakéhokoli postupu souvisejícího se studií.

Pro rameno 1 a 2 by měla být zvážena následující kritéria:

  • Pacienti s potvrzenou diagnózou MF, kteří splňují všechna následující kritéria
  • Riziková kategorie Dynamic International Prognostic Scoring System (DIPSS) střední-2 nebo vyšší
  • Objem sleziny ≥ 450 cm^3 podle MRI nebo CT pro kohorty 1B a 2B NEBO závislé na transfuzi červených krvinek (definováno jako průměr ≥2 jednotek transfuzí červených krvinek za měsíc (celkem více než 6 transfuzí červených krvinek) během 12 týdnů před zařazením pro kohorty 1A a 2A)
  • Alespoň 2 příznaky měřitelné (skóre ≥ 1) pomocí formuláře pro hodnocení symptomů myelofibrózy verze 4.0 (MFSAF v4.0)
  • Počet krevních destiček ≥ 75 x 10^9/l bez asistence trombopoetických faktorů nebo transfuzí po dobu nejméně 14 dnů
  • Rameno (rameno 1): Dříve léčeni inhibitorem JAK a být netolerantní, rezistentní, refrakterní nebo ztracená odpověď na inhibitor JAK; nedostávali inhibitor JAK během 2 týdnů před zahájením léčby studovaným lékem nebo nejsou způsobilí k léčbě inhibitorem JAK
  • Kombinované rameno (rameno 2): Musí dostávat ruxolitinib v monoterapii a být na stabilní dávce po dobu minimálně 8 týdnů, ale mít onemocnění, které není adekvátně kontrolováno ruxolitinibem

Pro rameno 3 (naivní inhibitory JAK) by měla být zvážena následující kritéria:

  • Pacienti s potvrzenou diagnózou MF, kteří splňují všechna následující kritéria
  • Riziková kategorie Dynamic International Prognostic Scoring System (DIPSS) střední-2 nebo vyšší
  • Počet krevních destiček ≥ 100 x 10^9/l bez pomoci trombopoetických faktorů nebo transfuzí
  • Objem sleziny ≥ 450 cm^3 podle MRI/CT
  • Alespoň 2 měřitelné příznaky (skóre ≥ 3) nebo celkové skóre ≥ 10 pomocí formuláře pro hodnocení symptomů myelofibrózy verze 4.0 (MFSAF v4.0)
  • Žádná předchozí léčba JAKi není povolena

Pro rameno 4 (ET Expansion) by měla být zvážena následující kritéria:

  • Pacienti s potvrzenou diagnózou ET
  • Vysoce rizikové onemocnění, definované jako splňující alespoň jedno z následujících kritérií:
  • Věk > 60 let
  • Počet krevních destiček > 1500 × 10^9/l (v kterémkoli okamžiku onemocnění pacienta)
  • Dříve dokumentovaná trombóza, erytromelalgie nebo migréna
  • Předchozí krvácení související s ET
  • Diabetes nebo hypertenze vyžadující farmakologickou léčbu po dobu > 6 měsíců

  • Mít ≥ 2 příznaky s průměrným skóre ≥ 3 během 7denního období před cyklem 1 Den 1 nebo průměrné celkové skóre ≥ 15 během 7denního období před cyklem 1 Den 1 pomocí použití MPN SAF

    • Krevní destičky > 600 × 10^9/l
    • Odolné nebo netolerantní vůči HU

Kritéria vyloučení:

  • Současná známá aktivní nebo chronická infekce virem lidské imunodeficience (HIV), hepatitidou B nebo hepatitidou C.
  • Porucha srdeční funkce nebo klinicky významná srdeční onemocnění
  • Pacienti s Child-Pugh třídou B nebo C
  • Porucha gastrointestinální (GI) funkce nebo onemocnění GI, které by mohlo významně změnit absorpci pelabresibu a/nebo ruxolitinibu, včetně jakékoli nevyřešené nevolnosti, zvracení nebo průjmu, které jsou stupně CTCAE >1
  • Předchozí léčba inhibitorem BET.
  • Těhotné nebo kojící ženy
  • Jakýkoli jiný souběžný závažný a/nebo nekontrolovaný doprovodný zdravotní stav, který by mohl ohrozit účast ve studii
  • Pacienti neochotní nebo neschopní dodržovat tento protokol studie.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Nerandomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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).
Lék: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ostatní jména:
  • CPI-0610
  • DAK539
Experimentální: 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).
Lék: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ostatní jména:
  • CPI-0610
  • DAK539
Experimentální: 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).
Lék: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ostatní jména:
  • CPI-0610
  • DAK539
Lék: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimentální: 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).
Lék: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ostatní jména:
  • CPI-0610
  • DAK539
Lék: Ruxolitinib
Ruxolitinib was given orally, twice daily (BID), on a continuous basis for 21 consecutive days of each 21-day cycle.
Experimentální: 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).
Lék: Pelabresib
CPI-0610 was administered orally once daily for 14 consecutive days, followed by a 7-day break (1 cycle = 21 days)
Ostatní jména:
  • CPI-0610
  • DAK539

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Phase 1: Frequency of Dose-limiting Toxicities (DLTs)
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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)

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Phase 1: Number of Adverse Events and Serious Adverse Events as Assessed by CTCAE Criteria
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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.

Další výstupní opatření

Měření výsledku
Časové okno
Fáze 2 (rameno 1, 2 a 3): Vyhodnoťte míru kategorie odezvy
Časové okno: Míra odpovědi Mezinárodní pracovní skupiny - Kritéria pro výzkum a léčbu myeloproliferativních novotvarů (IWG-MRT) po 24 týdnech
Míra odpovědi Mezinárodní pracovní skupiny - Kritéria pro výzkum a léčbu myeloproliferativních novotvarů (IWG-MRT) po 24 týdnech
Fáze 2 (rameno 1, 2 a 3): Vyhodnoťte rychlost transfuze červených krvinek a míru závislosti na transfuzi červených krvinek
Časové okno: Průměrný počet jednotek RBC na subjekt a měsíc, až 24 týdnů a déle
Průměrný počet jednotek RBC na subjekt a měsíc, až 24 týdnů a déle

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Constellation Pharmaceuticals

Spolupracovníci

The Leukemia and Lymphoma Society

Vyšetřovatelé

  • Ředitel studie: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Obecné publikace

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

16. července 2014

Primární dokončení (Aktuální)

9. ledna 2025

Dokončení studie (Aktuální)

9. ledna 2025

Termíny zápisu do studia

První předloženo

5. června 2014

První předloženo, které splnilo kritéria kontroly kvality

5. června 2014

První zveřejněno (Odhadovaný)

9. června 2014

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

4. června 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

8. května 2026

Naposledy ověřeno

1. dubna 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 0610-02
  • 2018-000579-34 (Číslo EudraCT)
  • CDAK539A12201 (Jiný identifikátor: Novartis)

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu IPD

Novartis se zavázala sdílet s kvalifikovanými externími vědci, přístup k údajům na úrovni pacienta a podporovat klinické dokumenty z způsobilých studií. Tyto žádosti jsou přezkoumány a schváleny nezávislým přezkumným panelem na základě vědeckých zásluh. Všechny poskytnuté údaje jsou anonymizovány, aby respektovaly soukromí pacientů, kteří se účastnili studie v souladu s platnými zákony a předpisy.

Tato zkušební dostupnost dat je podle kritérií a procesů popsaných na www.clinicalstudydarequest.com

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

produkt vyrobený a vyvážený z USA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

Klinické studie na Pelabresib

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