- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT01236352
Multiple Ascending Dose of BMS-911543
29 luglio 2019 aggiornato da: 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.
Panoramica dello studio
Tipo di studio
Interventistico
Iscrizione (Effettivo)
98
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Victoria
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East Melbourne, Victoria, Australia, 3002
- Local Institution
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Melbourne, Victoria, Australia, 3050
- Local Institution
-
-
-
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Minnesota
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Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic
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New York
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New York, New York, Stati Uniti, 10029
- The Mount Sinai School of Medicine
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Texas
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Houston, Texas, Stati Uniti, 77030
- The University of Texas MD Anderson Cancer Center
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
- Bambino
- Adulto
- Adulto più anziano
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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
|
Altri nomi:
|
Sperimentale: 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
|
Altri nomi:
|
Sperimentale: 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
|
Altri nomi:
|
Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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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Altri nomi:
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Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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
|
Altri nomi:
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Sperimentale: 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
|
Altri nomi:
|
Sperimentale: 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
|
Altri nomi:
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Number of Participants With Adverse Events
Lasso di tempo: 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).
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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
Lasso di tempo: 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.
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Day 1, at each returning on-treatment visit and the first post-treatment visit
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Changes in (Janus Kinase) JAK/Signal Transducers and Activators of Transcription (STATs) Pathway Activities, Circulating CD34+ Cells and Plasma Cytokine Levels
Lasso di tempo: 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)
Lasso di tempo: 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
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Trough Observed (Pre-dose) Plasma Concentration (Cmin) of BMS-911543 and it's Metabolite Met4
Lasso di tempo: 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
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Time of Maximum Observed Plasma Concentration (Tmax) of BMS-911543 and it's Metabolite Met4
Lasso di tempo: 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
Lasso di tempo: 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
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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
Lasso di tempo: 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
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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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
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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
Lasso di tempo: 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
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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
Lasso di tempo: 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
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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)
Lasso di tempo: 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
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Collegamenti utili
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
7 aprile 2011
Completamento primario (Effettivo)
19 novembre 2015
Completamento dello studio (Effettivo)
19 novembre 2015
Date di iscrizione allo studio
Primo inviato
5 novembre 2010
Primo inviato che soddisfa i criteri di controllo qualità
5 novembre 2010
Primo Inserito (Stima)
7 novembre 2010
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
31 luglio 2019
Ultimo aggiornamento inviato che soddisfa i criteri QC
29 luglio 2019
Ultimo verificato
1 luglio 2019
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Altri numeri di identificazione dello studio
- CA215-001
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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