Study of INCB053914 in Subjects With Advanced Malignancies
2021년 11월 9일 업데이트: Incyte Corporation
A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies.
The study will be conducted in 4 parts.
Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study).
Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s).
Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).
연구 개요
상태
종료됨
정황
연구 유형
중재적
등록 (실제)
97
단계
- 2 단계
- 1단계
확장된 액세스
승인됨 대중에게 판매합니다.
확장 액세스 기록을 참조하세요.
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Arizona
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Tucson, Arizona, 미국, 85719
- The University of Arizona Cancer Center
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California
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Sacramento, California, 미국, 95817
- UC Davis Comprehensive Cancer Center
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Santa Monica, California, 미국, 90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven, Connecticut, 미국, 06511
- Yale University
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Florida
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Jacksonville, Florida, 미국, 32224
- Mayo Clinic Florida
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Sarasota, Florida, 미국, 33916
- Florida Cancer Specialists & Research Institute
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Tampa, Florida, 미국, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Georgia
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Atlanta, Georgia, 미국, 30322
- Emory University-Winship Cancer Institute
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Maryland
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Baltimore, Maryland, 미국, 21201
- University of Maryland
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor, Michigan, 미국, 48109
- University of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha, Nebraska, 미국, 69198
- University Of Nebraska Medical Center
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Ohio
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Cincinnati, Ohio, 미국, 45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City, Oklahoma, 미국, 73104
- Stephenson Cancer Center
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Tennessee
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Nashville, Tennessee, 미국, 37232
- Vanderbilt University Medical Center
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Nashville, Tennessee, 미국, 37203
- Tennessee Oncology
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Texas
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Austin, Texas, 미국, 78705
- Texas Oncology
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Tyler, Texas, 미국, 75702
- Texas Oncology
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Wisconsin
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Milwaukee, Wisconsin, 미국, 53226
- Medical College of Wisconsin
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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
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Aged 18 years or older
- Confirmed diagnosis of select advanced malignancy
Parts 1 and 2:
- Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
- Not currently a candidate for curative treatment
Parts 3 and 4:
- Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Eastern Cooperative Oncology Group (ECOG) performance status
- Part 1: 0 or 1
- Parts 2, 3 and 4: 0, 1, or 2
- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.
Exclusion Criteria:
- Inadequate bone marrow or organ function
- Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
- Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
- Prior receipt of a PIM inhibitor
- Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
- Screening corrected QT interval (QTc) interval > 470 milliseconds
- Radiotherapy within the 2 weeks prior to initiation of treatment
- Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment
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: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Parts 1 and 2: INCB053914 100 mg QD
INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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실험적: Parts 3 and 4: INCB053914 + Azacitidine
Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Azacitidine dose will be 75 mg/m^2.
Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
다른 이름들:
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실험적: Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Cytarabine dose will be 1 g/m^2.
Cytarabine will be administered as an intravenous (IV) infusion.
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실험적: Parts 3 and 4: INCB053914 + Ruxolitinib
Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
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실험적: Parts 1 and 2: INCB053914 50 mg
INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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실험적: Parts 1 and 2: INB053914 65 mg
INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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실험적: Parts 1 and 2: INB053914 80 mg
INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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실험적: Parts 1 and 2: INB053914 100 mg BID
INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
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실험적: Parts 1 and 2: INB053914 115 mg
INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
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Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
기간: Approximately 7 months
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Approximately 7 months
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
기간: Approximately 2 months
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The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
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Approximately 2 months
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
기간: Approximately 6 months
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The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
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Approximately 6 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
기간: 1 month
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Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
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1 month
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Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
기간: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
기간: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
기간: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
기간: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
기간: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
기간: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
기간: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
기간: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
기간: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
기간: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
기간: Cycle 1 Day 8
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Cycle 1 Day 8
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 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)
2015년 12월 29일
기본 완료 (실제)
2020년 8월 11일
연구 완료 (실제)
2020년 8월 11일
연구 등록 날짜
최초 제출
2015년 10월 26일
QC 기준을 충족하는 최초 제출
2015년 10월 26일
처음 게시됨 (추정)
2015년 10월 27일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2021년 12월 8일
QC 기준을 충족하는 마지막 업데이트 제출
2021년 11월 9일
마지막으로 확인됨
2021년 11월 1일
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- INCB 53914-101
약물 및 장치 정보, 연구 문서
미국 FDA 규제 기기 제품 연구
아니
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. .