INCB000928 골수 증식성 질환으로 인한 빈혈이 있는 참여자에게 단일 요법으로 또는 Ruxolitinib과의 병용 요법으로 투여
골수증식성 질환으로 인한 빈혈 환자에게 단일 요법으로 또는 Ruxolitinib과 병용하여 투여된 INCB000928의 1/2상 공개 라벨, 다기관 연구
This Phase 1/2, open-label, dose-finding study is intended to evaluate the safety and tolerability, PK, PD, and efficacy of INCB000928 administered as monotherapy or in combination with ruxolitinib in participants with MF who are transfusion-dependent or presenting with symptomatic anemia. This study will consist of 2 parts: dose escalation and expansion.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
연구 유형
연구 유형
등록 (실제)
등록
단계
단계
- 2 단계
- 1단계
연락처 및 위치
연구 장소
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California
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Duarte, California, 미국, 91010
- City of Hope National Medical Center
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Irvine, California, 미국, 92618
- City of Hope Orange County
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Los Angeles, California, 미국, 90089
- Usc Norris Comprehensive Cancer Center
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Palo Alto, California, 미국, 94304
- Stanford Cancer Center
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San Diego, California, 미국, 92103
- Prebys Cancer Center
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Georgia
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Atlanta, Georgia, 미국, 30322
- Emory University - Winship Cancer Institute
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Atlanta, Georgia, 미국, 30322
- Emory University-Winship Cancer Institute
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Michigan
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Grand Rapids, Michigan, 미국, 49546
- Start Midwest
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Missouri
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St Louis, Missouri, 미국, 63110
- Washington University School of Medicine
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New York
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New York, New York, 미국, 10065
- Weill Cornell Medical Centers
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North Carolina
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Durham, North Carolina, 미국, 27705
- Duke University Medical Center, Department of Hematologic Malignancies and Cellular Therapy
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Tennessee
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Nashville, Tennessee, 미국, 37232
- Vanderbilt University Medical Center
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Texas
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Houston, Texas, 미국, 77030
- Md Anderson Cancer Center
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Boston, 영국, PE21 9QS
- United Lincolnshire Hospitals
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Lincoln, 영국, LN2 5QY
- Lincoln County Hospital
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Truro, 영국, TR1 3LJ
- Royal Cornwall Hospital Truro Sunrise Centre
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WLS
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Cardiff, WLS, 영국, CF14 4XW
- University Hospital of Wales
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Bergamo, 이탈리아, 24127
- Azienda Ospedaliera Papa Giovanni Xxiii
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Bologna, 이탈리아, 40138
- S Orsolas University Hospital Seragnoli Institute of Hematology
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Florence, 이탈리아, 50134
- Azienda Ospedaliero-Universitaria Careggi (Aouc)
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Orbassano, 이탈리아, 10043
- Azienda Ospedaliera Universitaria San Luigi Gonzaga Orbassano
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Pavia, 이탈리아, 27100
- Comitato Di Bioetica Della Fondazione Irccs Policlinico San Matteo
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Perugia, 이탈리아, 06124
- Ospedale Santa Maria Della Misericordia Perugia
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Bunkyō City, 일본, 113-8519
- Tokyo Medical and Dental University Hospital
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Chiba, 일본, 260-8717
- Chiba Cancer Center
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Gifu, 일본, 500-8513
- Gifu Municipal Hospital
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Hirakata, 일본, 573-1191
- Kansai Medical University Hospital
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Kumamoto, 일본, 862-8655
- Kumamoto Shinto General Hospital
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Osaka, 일본, 541-8567
- Osaka International Cancer Institute
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Ontario
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Toronto, Ontario, 캐나다, M5G 2M9
- Princess Margaret Cancer Center
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Quebec
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Montreal, Quebec, 캐나다, H3T1E2
- McGill University Jewish General Hospital
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Angers, 프랑스, 49033
- Centre Hospitalier D'Angers
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Marseille, 프랑스, 13273
- Institut Paoli Calmettes
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Paris, 프랑스, 75010
- Hospital Saint Louis
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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Participants with MF who are transfusion-dependent or present with symptomatic anemia, defined as follows:
- Anemia: An Hgb value < 10 g/dL demonstrated during screening recorded on 3 separate occasions with at least 7 days between measurements (Note: RBC transfusion must be at least 2 weeks before the Hgb measurement during screening).
- Transfusion-dependent: Participant has received at least 4 units of RBC transfusions during the 28 days immediately preceding Cycle 1 Day 1 OR has received an average of at least 4 units of RBC transfusions in the 8 weeks immediately preceding Cycle 1 Day 1, for an Hgb level of < 8.5 g/dL, in the absence of bleeding or treatment-induced anemia. In addition, the most recent transfusion episode must have occurred in the 28 days before Cycle 1 Day 1.
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ECOG performance status score of the following:
- 0 or 1 for the dose-escalation stages.
- 0, 1, or 2 for the dose-expansion stage.
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Life expectancy is greater than 6 months
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Agreement to avoid pregnancy or fathering children.
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Ineligible to receive or have not responded to available therapies for anemia such as ESAs.
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For TGA:
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Participants previously treated with JAK inhibitors for at least 12 weeks.
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Participants with intermediate-2 or high DIPSS MF according to IWG-MRT criteria.
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For TGB:
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Participants must have been on a therapeutic and stable regimen of ruxolitinib for at least 12 consecutive weeks immediately preceding the first dose of study treatment.
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Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.
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For TGC:
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Participants must be JAK inhibitor treatment naive (no prior treatment with any JAK inhibitor) and have an indication for initiation of ruxolitinib treatment.
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Participants with intermediate-1, intermediate-2, or high DIPSS MF according to IWG-MRT criteria.
Exclusion Criteria:
- Undergone any prior allogenic or autologous stem cell transplantation or a candidate for such transplantation.
- Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody or hypomethylating agent to treat the participant's disease, with the exception of ruxolitinib for TGB only, within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment.
- Laboratory Values outside of protocol defined range at screening.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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실험적: Treatment Group A (TGA)
INCB000928 will be administered once daily (QD). |
INCB000928 will be administered at protocol defined dose. |
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실험적: Treatment Group B (TGB)
INCB000928 will be administered in combination with ruxolitinib. |
INCB000928 will be administered at protocol defined dose. Ruxolitinib will be administered at protocol defined dose. |
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실험적: Treatment Group C (TGC)
INCB000928 will be administered in combination with ruxolitinib. |
INCB000928 will be administered at protocol defined dose. Ruxolitinib will be administered at protocol defined dose. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Treatment-emergent Serious Adverse Event (SAE)
기간: up to approximately 4 years
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An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug/treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. |
up to approximately 4 years
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Number of Participants With Any ≥Grade 3 TEAE and Any Treatment-emergent SAE
기간: up to approximately 4 years
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An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grades 1 through 5. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
up to approximately 4 years
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Number of Participants With Dose-limiting Toxicities (DLTs)
기간: from Cycle 1 Day 1 to Cycle 1 Day 28
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A DLT was defined as the occurrence of any protocol-defined toxicity occurring during the first treatment cycle, from Cycle 1 Day 1 up to and including Cycle 1 Day 28 (per regimen cycle schedule), except those with a clear alternative explanation (e.g., disease progression) or transient (≤72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. The DLT-Evaluable Population included all non-backfill participants eligible for dose escalation who met the criteria outlined in the Analysis Population field. |
from Cycle 1 Day 1 to Cycle 1 Day 28
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Maximum Tolerated Dose (MTD)
기간: from Cycle 1 Day 1 to Cycle 1 Day 28
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The MTD was defined as the dose at which the observed DLT rate was closest to the target DLT rate of 28% using an isotonical method that took the assumption of a monotonic dose-toxicity relationship into account. Per the protocol, the stopping rule was either (a) reaching a certain number of participants at one dose level under the early stopping rule or (b) reaching the pre-defined maximum sample size. Dose escalation was to be considered complete only when one of these conditions was met. After completion, the MTD was to be defined as the dose level closest to the target DLT rate. The MTD could not be concluded until the stopping rule was met. |
from Cycle 1 Day 1 to Cycle 1 Day 28
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Recommended Dose for Expansion (RDE)
기간: from Cycle 1 Day 1 to Cycle 1 Day 28
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The RDE was defined as a pharmacodynamically active dose. The RDE was determined in an independent fashion by evaluation of all available data (i.e., safety, pharmacokinetic, and pharmacodynamic data) from the respective dose-escalation stage of the study for further investigation in the expansion cohort, including safety (e.g., low-grade but chronic toxicities, dose reduction, dose interruption, or missed doses of zilurgisertib and/or ruxolitinib). The RDE(s) could not exceed the MTD in each treatment group |
from Cycle 1 Day 1 to Cycle 1 Day 28
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of Participants With Anemia Response
기간: up to Week 24
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Anemia response was defined as (a) a hemoglobin (Hgb) increase of 1.5 grams per deciliter (g/dL) relative to baseline for any "rolling" 12-week period (84 days with each assessment that met this requirement) during the first 24 weeks of treatment if transfusion independent (TI) at baseline; or (b) transfusion independence for any "rolling" 12-week period (absence of any red blood cell [RBC] transfusion over any 84-day period) during the first 24 weeks of treatment if transfusion dependent (TD) at baseline. |
up to Week 24
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Duration of Anemia Response
기간: up to 1530 days
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Duration of anemia response was defined as (a) the interval from the first onset of anemia response to the earliest date of loss of anemia response that persisted for at least 4 weeks or death from any cause (for TI participants at baseline); or (b) the duration of the RBC-TI period for participants who achieved RBC-TI for at least 12 consecutive weeks during the first 24 weeks of treatment (for TD participants at baseline). |
up to 1530 days
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Mean Change From Baseline in the Hgb Value Over 12-week Treatment Periods
기간: Baseline; up to 24 weeks
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Mean change from baseline was assessed as the largest increase from baseline in the mean Hgb values over any rolling 12-week treatment period during the first 24 weeks of treatment. Change from baseline was calculated as the post-baseline value minus the baseline value. |
Baseline; up to 24 weeks
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Rate of Red Blood Cell (RBC) Transfusion From Week 24 Through Week 48
기간: from Week 24 through Week 48
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The rate of RBC transfusion was defined as the average number of RBC units per participant-month during the treatment period. |
from Week 24 through Week 48
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Splenic Volume Response Rate at Week 24
기간: Week 24
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Splenic volume response rate was defined as the percentage of participants achieving a ≥35% reduction in spleen volume at Week 24 relative to baseline as measured by magnetic resonance imaging or computed tomography scan. |
Week 24
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Spleen Length Response
기간: Week 24
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Spleen length response was defined as the percentage of participants achieving a ≥50% reduction in spleen length at any visit relative to baseline as measured by palpation. |
Week 24
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Overall Response Rate (ORR)
기간: Week 24
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ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) (including the morphologic effects of the combination of zilurgisertib with ruxolitinib on bone marrow) according to Tefferi et al (2013) definitions. |
Week 24
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Progression-free Survival (PFS)
기간: Week 24
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PFS was defined as the interval from the first dose of study treatment until the first documented progression or death according to Tefferi et al (2013) definitions. |
Week 24
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Leukemia-free Survival (LFS)
기간: Week 24
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LFS was defined as the interval from the first dose of study treatment until the first documented leukemia transformation or death from any cause. |
Week 24
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Cmax of Zilurgisertib Alone
기간: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
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Cmax was defined as the maximum concentration of zilurgisertib. |
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
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Tmax of Zilurgisertib
기간: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
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tmax was defined as the time to the maximum concentration of zilurgisertib. |
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
|
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AUC0-t of Zilurgisertib
기간: Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
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AUC0-t was defined as the area under the plasma concentration-time curve from time 0 to the last quantifiable measurable plasma concentration of zilurgisertib. |
Cycle 1 Day 1 (first dose) and Cycle 1 Day 15 (steady state): pre-dose and 2 hours, 4 hours, and 6-8 hours post-dose
|
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Percentage Change in Hepcidin From Cycle 1 Day 15 to Cycle 7 Day 1
기간: from Cycle 1 Day 15 to Cycle 7 Day 1
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Percentage change was calculated as the ([post-baseline value minus the baseline value] / [baseline value]) * 100. |
from Cycle 1 Day 15 to Cycle 7 Day 1
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Change From Baseline in Ferritin
기간: Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
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Change from Baseline (CFB) was calculated as the post-Baseline value minus the Baseline value. |
Baseline; Cycle 1 Day 8; Cycle 1 Day 15; Cycle 1 Day 22; Cycles 2, 3, 4, 5, 6, and 7 Day 1; Cycle 2 Day 15
|
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Change From Baseline in Hemoglobin at the End of Treatment
기간: up to 1530 days
|
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
up to 1530 days
|
공동 작업자 및 조사자
수사관
수사관
- 연구 책임자: Amanda McBride, MD, Incyte Corporation
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (실제)
기본 완료
연구 완료 (실제)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- INCB 00928-104
- 2020-004029-21 (EudraCT 번호)
- 2023-503625-19-00 (레지스트리 식별자: EU CT Number)
- 2023 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
IPD 공유 기간
Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
IPD 공유 액세스 기준
Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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. .