Multiple Ascending Dose of BMS-911543
2019년 7월 29일 업데이트: 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.
연구 개요
연구 유형
중재적
등록 (실제)
98
단계
- 2 단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Minnesota
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Rochester, Minnesota, 미국, 55905
- Mayo Clinic
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New York
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New York, New York, 미국, 10029
- The Mount Sinai School of Medicine
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Texas
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Houston, Texas, 미국, 77030
- The University of Texas MD Anderson Cancer Center
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Victoria
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East Melbourne, Victoria, 호주, 3002
- Local Institution
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Melbourne, Victoria, 호주, 3050
- Local Institution
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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실험적: 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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다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Number of Participants With Adverse Events
기간: 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
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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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
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2011년 4월 7일
기본 완료 (실제)
2015년 11월 19일
연구 완료 (실제)
2015년 11월 19일
연구 등록 날짜
최초 제출
2010년 11월 5일
QC 기준을 충족하는 최초 제출
2010년 11월 5일
처음 게시됨 (추정)
2010년 11월 7일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 7월 31일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 7월 29일
마지막으로 확인됨
2019년 7월 1일
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- CA215-001
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
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Bristol-Myers Squibb모집하지 않고 적극적으로진행성 폐 섬유증프랑스, 포르투갈, 독일, 헝가리, 미국, 아르헨티나, 호주, 오스트리아, 벨기에, 브라질, 캐나다, 칠레, 중국, 콜롬비아, 체코, 덴마크, 핀란드, 그리스, 인도, 아일랜드, 이스라엘, 이탈리아, 일본, 말레이시아, 멕시코, 네덜란드, 페루, 폴란드, 푸에르토 리코, 대한민국, 스페인, 스위스, 대만, 터키 (Türkiye), 영국
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