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Multiple Ascending Dose of BMS-911543

29 lipca 2019 zaktualizowane przez: Bristol-Myers Squibb

A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BMS-911543 in Subjects With Myelofibrosis

The purpose of this first in human study is to determine if BMS-911543 is safe and tolerable in subjects with symptomatic intermediate-1, intermediate-2 or high risk myelofibrosis to permit clinical testing at the Maximum Tolerated Dose or at a Clinically Active Dose, and to determine if BMS-911543 will demonstrate efficacy in symptomatic myelofibrosis.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

98

Faza

  • Faza 2
  • Faza 1

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Local Institution
      • Melbourne, Victoria, Australia, 3050
        • Local Institution
  • Stany Zjednoczone
    • Minnesota
      • Rochester, Minnesota, Stany Zjednoczone, 55905
        • Mayo Clinic
    • New York
      • New York, New York, Stany Zjednoczone, 10029
        • The Mount Sinai School of Medicine
    • Texas
      • Houston, Texas, Stany Zjednoczone, 77030
        • The University of Texas MD Anderson Cancer Center

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dziecko
  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Men and Women at least 18 years old
  • A diagnosis of symptomatic, primary or secondary Myelofibrosis (MF) [World Health Organization (WHO) 2008 criteria] with intermediate-1, intermediate-2 or high risk disease as assessed using the Dynamic International Prognostic Scoring System international prognostic scoring system
  • Last therapeutic or diagnostic treatment at least 28 days prior
  • Any toxicity from prior therapies must have resolved to Grade ≤1
  • Adequate Liver and Kidney Function
  • Serum amylase and lipase within normal institutional range
  • Platelet count ≥50,000 cell mm³
  • Absolute neutrophil count (ANC) ≥1,000 cells/mm3
  • Hemoglobin ≥8.0 g/dL

Exclusion Criteria:

  • Primary central nervous system tumors
  • Subjects with currently active malignancy (other than MF) or with a prior history of malignancy with the exception of: (i) adequately treated basal cell carcinoma of the skin, (ii) curatively treated in situ carcinoma of the cervix, (iii) other malignancy that has undergone potentially curative therapy with no evidence of disease recurrence ≥3 years
  • Any condition requiring chronic use of moderate/high dose steroids except inhalation or oral steroids for mild pulmonary disease
  • Splenic irradiation ≤3 months prior to treatment with study drug
  • Positive blood screen for hepatitis C antibody, hepatitis B surface antigen or Human Immunodeficiency Virus-1 (HIV-1), or HIV-2 antibodies
  • Abnormalities in serum electrolytes
  • Significant cardiovascular disease
  • Current or recent gastrointestinal disease
  • Previous history of pancreatitis and/or significant risk factors for pancreatitis as judged by the treating physician
  • Evidence of uncontrolled active infection or active graft vs. host disease
  • Inability to tolerate oral medication

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Nielosowe
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Brak (otwarta etykieta)

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Phase 1 (Cohort 1): BMS-911543 (5 mg)
BMS-911543 5 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 2): BMS-911543 (10 mg)
BMS-911543 10 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 3): BMS-911543 (20 mg)
BMS-911543 20 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 4): BMS-911543 (40 mg)
BMS-911543 40 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 5): BMS-911543 (80 mg)
BMS-911543 80 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 6): BMS-911543 (120 mg)
BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 7): BMS-911543 (160 mg)
BMS-911543 160 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 8): BMS-911543 (200 mg)
BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 9): BMS-911543 (240 mg)
BMS-911543 240 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 1 (Cohort 10): BMS-911543 (320 mg)
BMS-911543 320 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 2 (Cohort 11): BMS-911543 (120 mg)
BMS-911543 120 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2
Eksperymentalny: Phase 2 (Cohort 12): BMS-911543 (200 mg)
BMS-911543 200 mg capsule by mouth twice daily for 12 months or greater depending on response
Lek: BMS-911543
Inne nazwy:
  • Inhibitor JAK2

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Number of Participants With Adverse Events
Ramy czasowe: From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
Safety assessments were based on a medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests and were evaluated for all treated participants using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (NCI CTCAE v.4.0).
From the date of participant's written consent until 30 days post discontinuation of dosing or participation in the study if the last scheduled visit occured at a later time, assessed up to 4.5 years
Number of Participants With Best Overall Response
Ramy czasowe: Day 1, at each returning on-treatment visit and the first post-treatment visit
Participants were clinically assessed for IWG-(International Working Group consensus criteria for treatment response in myelofibrosis with myeloid metaplasia) defined response at each returning on-treatment visit and the first post-treatment visit. IWG-MRT criteria for best overall response are ordered high to low: CR>PR>CI>SD>PD>R where CR = Complete Remission, PR= Partial Remission, CI = Clinical Improvement, SD = Stable Disease, PD = Progressive Disease and R = Relapse. Best overall response is the best response of the subject during the treatment period or at the first post-treatment visit.
Day 1, at each returning on-treatment visit and the first post-treatment visit

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Ramy czasowe: Up to 6 months
JAK/STAT pathway activity will be evaluated by: 1) pSTATs levels using immunoassay; 2) expression levels of several JAK/STATs pathway genes. Whole blood will be collected at specific time-points. Due to portfolio/business decisions by the sponsor, the compound is no longer being developed and the study was terminated. Analysis was not completed because the study was terminated. This decision was not based on any safety concerns associated with BMS-911543.
Up to 6 months
Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmax Maximum observed plasma concentration
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Cmin (Trough observed (pre-dose) plasma concentration)
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Tmax = Time of maximum observed plasma concentration (Tmax) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time (for Single Dose Period Only) (AUC(INF)) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC(INF) = Area under the plasma concentration-time curve from time zero extrapolated to infinite time (for single dose period only) (AUC(INF)) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Plasma Concentration (for Single Dose Period Only) (AUC(0-T)) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (0-T) = Area under the plasma concentration-time curve from time zero to the time of last quantifiable plasma concentration (for single dose period only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC (TAU) = Area under the concentration-time curve in one dosing interval of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: T-HALF = The terminal-phase elimination half-life in plasma of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: CLT/F = Apparent total clearance (for parent compound only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Apparent Volume of Distribution After First Dosing Based on the Terminal Phase (for Parent Compound Only) (Vz/F) of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Vz/F = Apparent volume of distribution after first dosing based on the terminal phase (for parent compound only) of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Accumulation Index (AI): Ratio of AUC(TAU) on Day 15 to AUC(TAU) After the First Dose of BMS-911543 and it's Metabolite Met4
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: Accumulation index (AI) = ratio of AUC(TAU) on Day 15 to AUC(TAU) after the first dose of BMS-911543 and it's metabolite Met4
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) After 1st Dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15 (AUC Ratio)
Ramy czasowe: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
Pharmacokinetic parameters of BMS-911543 and BMS-926796 (Met4) metabolite, will be derived from plasma concentration versus time. The pharmacokinetic parameters to be assessed include: AUC Ratio = Ratio of BMS-926796 AUC(INF) to BMS-911543 AUC(INF) after 1st dose and BMS-926796 AUC(TAU) to BMS-911543 AUC(TAU) on Day 15
Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Bristol-Myers Squibb

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Przydatne linki

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Rzeczywisty)

7 kwietnia 2011

Zakończenie podstawowe (Rzeczywisty)

19 listopada 2015

Ukończenie studiów (Rzeczywisty)

19 listopada 2015

Daty rejestracji na studia

Pierwszy przesłany

5 listopada 2010

Pierwszy przesłany, który spełnia kryteria kontroli jakości

5 listopada 2010

Pierwszy wysłany (Oszacować)

7 listopada 2010

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

31 lipca 2019

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

29 lipca 2019

Ostatnia weryfikacja

1 lipca 2019

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Inne numery identyfikacyjne badania

  • CA215-001

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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