Multiple Ascending Dose of BMS-911543
2019. július 29. frissítette: 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.
A tanulmány áttekintése
Tanulmány típusa
Beavatkozó
Beiratkozás (Tényleges)
98
Fázis
- 2. fázis
- 1. fázis
Kapcsolatok és helyek
Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.
Tanulmányi helyek
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Victoria
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East Melbourne, Victoria, Ausztrália, 3002
- Local Institution
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Melbourne, Victoria, Ausztrália, 3050
- Local Institution
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Minnesota
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Rochester, Minnesota, Egyesült Államok, 55905
- Mayo Clinic
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New York
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New York, New York, Egyesült Államok, 10029
- The Mount Sinai School of Medicine
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Texas
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Houston, Texas, Egyesült Államok, 77030
- The University of Texas MD Anderson Cancer Center
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Részvételi kritériumok
A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.
Jogosultsági kritériumok
Tanulmányozható életkorok
- Gyermek
- Felnőtt
- Idősebb felnőtt
Egészséges önkénteseket fogad
Nem
Tanulmányozható nemek
Összes
Leírás
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
Tanulási terv
Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Nem véletlenszerű
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Kísérleti: 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
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Más nevek:
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Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Number of Participants With Adverse Events
Időkeret: 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
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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).
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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
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Number of Participants With Best Overall Response
Időkeret: Day 1, at each returning on-treatment visit and the first post-treatment visit
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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.
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Day 1, at each returning on-treatment visit and the first post-treatment visit
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Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
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Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Időkeret: Up to 6 months
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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.
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Up to 6 months
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Maximum Observed Plasma Concentration (Cmax) of BMS-911543 and it's Metabolite BMS-926796 (Met4)
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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)
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) of BMS-911543 and it's Metabolite Met4
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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The Terminal-phase Elimination Half-life in Plasma (T-HALF) of BMS-911543 and it's Metabolite Met4
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Apparent Total Clearance (for Parent Compound Only) (CLT/F) of BMS-911543 and it's Metabolite Met4
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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)
Időkeret: Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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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
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Day -1, Day 1, Day 8, Day 15, Day 21 and Day 28 or off-study
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Együttműködők és nyomozók
Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.
Szponzor
Publikációk és hasznos linkek
A vizsgálattal kapcsolatos információk beviteléért felelős személy önkéntesen bocsátja rendelkezésre ezeket a kiadványokat. Ezek bármiről szólhatnak, ami a tanulmányhoz kapcsolódik.
Tanulmányi rekorddátumok
Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
2011. április 7.
Elsődleges befejezés (Tényleges)
2015. november 19.
A tanulmány befejezése (Tényleges)
2015. november 19.
Tanulmányi regisztráció dátumai
Először benyújtva
2010. november 5.
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
2010. november 5.
Első közzététel (Becslés)
2010. november 7.
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
2019. július 31.
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
2019. július 29.
Utolsó ellenőrzés
2019. július 1.
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
Egyéb vizsgálati azonosító számok
- CA215-001
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .