- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT04021368
급성 골수성 백혈병 또는 고위험 골수이형성 증후군 환자의 RVU120
급성 골수성 백혈병 또는 고위험 골수이형성 증후군 환자를 대상으로 한 RVU120(SEL120)의 Ib상 연구
This first-in-human study will evaluate RVU120 (SEL120), a novel small molecule CDK8/19 inhibitor, in patients with Acute Myeloid Leukemia (AML) or High-risk Myelodysplastic Syndrome (HR-MDS), in terms of selection of the recommended dose for further clinical development and assessment of safety, tolerability, preliminary anti-leukemic activity, as well as pharmacokinetic and pharmacodynamic profiles.
연구 개요
상세 설명
The study will determine the recommended phase II dose (RP2D) and safety of RVU120 (SEL120) given as monotherapy over a range of dose-levels, following a closely controlled dose escalation study design.
연구 유형
등록 (실제)
단계
- 1단계
연락처 및 위치
연구 장소
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Florida
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Miami, Florida, 미국, 33136
- Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics
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Georgia
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Atlanta, Georgia, 미국, 30342
- Northside Hospital
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Missouri
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St Louis, Missouri, 미국, 63110
- Washington University School of Medicine
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Tennessee
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Nashville, Tennessee, 미국, 37203
- Tennessee Oncology
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Texas
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Houston, Texas, 미국, 77030
- MD Anderson Cancer Center
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Gdansk, 폴란드, 80-214
- Uniwersyteckie Centrum Kliniczne
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Torun, 폴란드, 87-100
- MICS Centrum Medyczne Toruń
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Warsaw, 폴란드, 02-776
- Instytut Hematologii i Transfuzjologii
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Wroclaw, 폴란드, 53-413
- Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii
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Świętokrzyskie Voivodeship
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Kielce, Świętokrzyskie Voivodeship, 폴란드, 25-734
- Świętokrzyskie Centrum Onkologii, Klinika Hematologii i Transplantacji Szpiku
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
All the following criteria must be met for a patient to be eligible for the study:
- Written informed consent provided prior to any study-related procedure.
- Age ≥18 years.
- AML diagnosis according to the 2016 World Health Organisation (WHO) classification (Arber et al. 2016) with relapsed or refractory disease with no available therapy who have exhausted the applicable standard of care; or Myelodysplastic Syndrome (MDS) diagnosis according to the 2016 WHO classification (Arber et al. 2016) with high-risk disease per the Revised International Prognostic Scoring System (IPSS-R >4.5) and with relapsed or refractory disease with no available therapy who have exhausted the applicable standard of care.
- Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
- Patients must have been off anti-cancer treatment prior to study.
- Patients must have recovered from the toxic effects of previous treatments.
- Peripheral white blood cell (WBC) count <10x10^9/L; Platelet count >10,000/μL; Serum albumin ≥ 30g/L (3.0g/dL); Normal coagulation (elevated INR, prothrombin time or APTT <1.3 x ULN acceptable); AST and ALT ≤3x ULN; Total bilirubin ≤1.5 x ULN; Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula);
- Adequate cardiac function
- Life expectancy of at least 12 weeks.
- For females of childbearing potential (FCBP), a negative pregnancy test must be confirmed before enrolment. FCBP must commit to use a highly effective method of contraception during study participation and until 6 months after the last dose of study drug. Females must also refrain from donating blood or egg (ovum) during the same time period.
- For males, an effective barrier method of contraception must be used during study participation until 6 months after the last dose of study drug, if the patient is sexually active with a FCBP. Males must also refrain from donating blood or sperm during the same time-period.
- Investigator considers the patient to be suitable for participation in the clinical study
Exclusion Criteria:
- Active central nervous system (CNS) leukemia.
- Previous treatment with CDK8-targeted therapy.
- Patients who have undergone major surgery within 28 days prior to first dose of study drug.
- Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
- Active acute graft versus host disease (GVHD)
- Infections and acute inflammatory conditions
- Known seropositivity or history of HIV
- Known positive test of / or known active diagnosis of COVID-19 viral infection
- Ongoing significant liver disease
- Impairment of gastrointestinal function or gastrointestinal disease
- Ongoing drug-induced pneumonitis.
- Concurrent participation in another investigational clinical trial.
- Taking any medications, herbal supplements or other substances (including smoking) that are known to be strong inhibitors or inducers of CYP1A2 or that can prolong Q wave to T wave (QT) interval and/or cause torsade de pointes within less than 5 half-lives, prior to first dose of study drug.
- Significant cardiac dysfunction or poorly controlled angina.
- Currently taking drugs that are documented, in the drug package insert, to have a risk of causing prolonged QTc or torsades de pointes (TdP) within 5 half-lives prior to first dose of study drug.
- Personal or family history of serious ventricular arrhythmia, or QT interval corrected for heart rate (QTc) ≥470 ms (Bazett's formula).
- Any other prior or current medical condition or extenuating circumstance that, in the Investigator's opinion, could jeopardize patient safety or interfere with the objectives of the study.
- Prior history of malignancies other than AML or MDS, unless the patient has been free of the disease for 5 years or more prior to Screening.
- Pregnant or breast-feeding females.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: RVU120(SEL120)
The first part of the study consists of dose-escalation cohorts where patients will receive ascending doses of RVU120(SEL120) to determine the recommended dose (RD) for further clinical development. The second part of the study is an enrichment cohort where additional 6 to 20 patients will be treated with RVU120(SEL120) to support the evaluation of the RD. |
RVU120(SEL120) will be administered as a single oral dose every other day (q.o.d.) for a total of 7 doses i.e. on Days 1, 3, 5, 7, 9, 11 and 13, in a 3-week treatment cycle. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Recommended dose (RD)
기간: Up to 2 years
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The RD will be determined using all available data, which will include dose limiting toxicities (DLTs) and other toxicities, signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics. |
Up to 2 years
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Incidence of Adverse Events (Safety and Tolerability)
기간: Up to 2 years
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Safety and tolerability profile will be assessed by Common Terminology Criteria for Adverse Events v5.0 and summarized by type, frequency, and severity of adverse events. |
Up to 2 years
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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The Maximum Observed Concentration (C[max])
기간: Up to 2 years
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Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Maximum Observed Concentration (C[max]). |
Up to 2 years
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The Terminal Half-life (t[1/2])
기간: Up to 2 years
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Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Terminal Half-life (t[1/2]). |
Up to 2 years
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The Area Under the Curve (AUC)
기간: Up to 2 years
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Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Area Under the Curve (AUC). |
Up to 2 years
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The Volume of Distribution at Steady State (Vss)
기간: Up to 2 years
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Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Volume of Distribution at Steady State (Vss). |
Up to 2 years
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Anti-leukemic activity
기간: Up to 2 years
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Anti-leukemic activity will be assessed by AML or MDS Response Criteria (Döhner et al., 2017, or Cheson et al., 2006, respectively). |
Up to 2 years
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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AML surface markers
기간: Up to 2 years
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Pharmacodynamic profile of RVU120(SEL120) will be characterized using immunophenotyping of AML surface markers by exploratory assay. |
Up to 2 years
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Phosphorylated protein levels in AML blasts
기간: Up to 2 years
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Pharmacodynamic profile of RVU120(SEL120) will be characterized using phosphorylated protein levels in AML blasts by exploratory immunoassay. |
Up to 2 years
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Transcriptomic profile changes in AML blasts
기간: Up to 2 years
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Pharmacodynamic profile of RVU120(SEL120) will be characterized using transcriptomic profile changes in AML blasts by exploratory next generation sequencing. |
Up to 2 years
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Genetic profile changes in AML blasts
기간: Up to 2 years
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Pharmacodynamic profile of RVU120(SEL120) will be characterized using genetic profile changes in AML blasts by next generation sequencing. |
Up to 2 years
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공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- CLI120-001
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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