이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

급성 골수성 백혈병 및 골수이형성 증후군 환자의 결과를 개선하기 위해 항암제인 Cirtuvivint 및 ASTX727 및 ASTX727과 Venetoclax의 병용 테스트

2026년 10월 31일 업데이트: National Cancer Institute (NCI)

골수이형성증후군(MDS) 및 급성 골수성 백혈병(AML) 환자를 대상으로 단일요법 및 ASTX727 및 ASTX727 + 베네토클락스와의 병용 요법으로 서투비빈트의 안전성을 평가하는 1상 연구

This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727 in treating patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Cirtuvivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Giving cirtuvivint alone or in combination with ASTX727 may be safe, tolerable, and/or effective in treating patients with AML and MDS.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

PRIMARY OBJECTIVE:

I. To determine the recommended phase 2 dose (RP2D) of SM08502 (cirtuvivint) as monotherapy in relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) (Cohort I and II) and in combination with decitabine and cedazuridine (ASTX727) in frontline MDS (Cohort III).

SECONDARY OBJECTIVES:

I. To assess the safety/tolerability of SM08502 (cirtuvivint) as monotherapy in R/R AML and MDS (Cohort I and II) and in combination with ASTX727 in frontline MDS (Cohort III).

II. To assess the pharmacokinetics (PK), and pharmacodynamics (PD) of SM08502 (cirtuvivint) as monotherapy in R/R AML and MDS (Cohort I and II) and in combination with ASTX727 in frontline MDS (Cohort III).

III. To determine the preliminary efficacy of the combination of SM08502 (cirtuvivint) as monotherapy in R/R AML and MDS (Cohort I and II) and in combination with ASTX727 in frontline MDS (Cohort III) by assessing the response rate as defined by the 2022 European LeukemiaNet (ELN) response criteria for AML (Döhner et al., 2022) and International Working Group (IWG) 2023 response criteria for MDS (Zeidan et al., 2023).

IV. To explore survival outcomes achieved with SM08502 (cirtuvivint) as monotherapy in R/R AML and MDS (Cohort I and II) and in combination with ASTX727 in frontline MDS (Cohort III) by assessing 1 year event free survival (EFS) and overall survival (OS) rate.

V. To observe and record anti-tumor activity. VI. To evaluate the best schedule to move forward with in Phase 2.

OUTLINE: This is a dose-escalation study of cirtuvivint as monotherapy. Patients are assigned to 1 of 3 cohorts.

COHORT I: Patients receive cirtuvivint orally (PO) once daily (QD) on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

COHORT II: Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

COHORT III: Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 and ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.

After completion of study treatment, patients are followed up for 30 days, every 3 months for 2 years then every 6 months for up to 3 years.

연구 유형

중재적

등록 (추정된)

단계

1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

미국
- Connecticut
  - New Haven, Connecticut, 미국, 06520
    - 모병
    - Yale University
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 203-785-5702
      
      이메일: canceranswers@yale.edu
    - 수석 연구원:
      
      Maximilian Stahl
- Georgia
  - Atlanta, Georgia, 미국, 30322
    - 모병
    - Emory University Hospital/Winship Cancer Institute
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 404-778-1868
    - 수석 연구원:
      
      Michael J. Hochman
- Illinois
  - Chicago, Illinois, 미국, 60637
    - 모병
    - University of Chicago Comprehensive Cancer Center
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 773-702-8222
      
      이메일: cancerclinicaltrials@bsd.uchicago.edu
    - 수석 연구원:
      
      Olatoyosi M. Odenike
  - New Lenox, Illinois, 미국, 60451
    - 정지된
    - UC Comprehensive Cancer Center at Silver Cross
  - Orland Park, Illinois, 미국, 60462
    - 정지된
    - University of Chicago Medicine-Orland Park
- Indiana
  - Crown Point, Indiana, 미국, 46307
    - 정지된
    - UChicago Medicine Northwest Indiana
- Maryland
  - Baltimore, Maryland, 미국, 21287
    - 모병
    - Johns Hopkins University/Sidney Kimmel Cancer Center
    - 수석 연구원:
      
      Ivana Gojo
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 410-955-8804
      
      이메일: jhcccro@jhmi.edu
  - Baltimore, Maryland, 미국, 21201
    - 모병
    - University of Maryland/Greenebaum Cancer Center
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-888-8823
    - 수석 연구원:
      
      Vu H. Duong
- Massachusetts
  - Boston, Massachusetts, 미국, 02215
    - 모병
    - Dana-Farber Cancer Institute
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 877-442-3324
    - 수석 연구원:
      
      Evan C. Chen
- Missouri
  - City of Saint Peters, Missouri, 미국, 63376
    - 모병
    - Siteman Cancer Center at Saint Peters Hospital
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-600-3606
      
      이메일: info@siteman.wustl.edu
    - 수석 연구원:
      
      Meagan Jacoby
  - Creve Coeur, Missouri, 미국, 63141
    - 모병
    - Siteman Cancer Center at West County Hospital
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-600-3606
      
      이메일: info@siteman.wustl.edu
    - 수석 연구원:
      
      Meagan Jacoby
  - St Louis, Missouri, 미국, 63110
    - 모병
    - Washington University School of Medicine
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-600-3606
      
      이메일: info@siteman.wustl.edu
    - 수석 연구원:
      
      Meagan Jacoby
  - St Louis, Missouri, 미국, 63129
    - 모병
    - Siteman Cancer Center-South County
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-600-3606
      
      이메일: info@siteman.wustl.edu
    - 수석 연구원:
      
      Meagan Jacoby
  - St Louis, Missouri, 미국, 63136
    - 모병
    - Siteman Cancer Center at Christian Hospital
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 800-600-3606
      
      이메일: info@siteman.wustl.edu
    - 수석 연구원:
      
      Meagan Jacoby
- New Jersey
  - Basking Ridge, New Jersey, 미국, 07920
    - 모병
    - Memorial Sloan Kettering Basking Ridge
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - Middletown, New Jersey, 미국, 07748
    - 모병
    - Memorial Sloan Kettering Monmouth
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - Montvale, New Jersey, 미국, 07645
    - 모병
    - Memorial Sloan Kettering Bergen
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - New Brunswick, New Jersey, 미국, 08903
    - 모병
    - Rutgers Cancer Institute of New Jersey
    - 수석 연구원:
      
      Neil D. Palmisiano
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 732-235-7356
- New York
  - Commack, New York, 미국, 11725
    - 모병
    - Memorial Sloan Kettering Commack
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - Harrison, New York, 미국, 10604
    - 모병
    - Memorial Sloan Kettering Westchester
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - New York, New York, 미국, 10065
    - 모병
    - Memorial Sloan Kettering Cancer Center
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
  - Uniondale, New York, 미국, 11553
    - 모병
    - Memorial Sloan Kettering Nassau
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 212-639-7592
    - 수석 연구원:
      
      Tamanna Haque
- North Carolina
  - Winston-Salem, North Carolina, 미국, 27157
    - 모병
    - Wake Forest University Health Sciences
    - 연락하다:
      
      Site Public Contact
      
      전화번호: 336-713-6771
    - 수석 연구원:
      
      Madelyn Burkart

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:

In Cohorts I and II, patients must have R/R AML or MDS (venetoclax naïve or venetoclax exposed)
- Relapsed AML is defined as the appearance of 5% or greater myeloblasts in the bone marrow or peripheral blood after achieving a complete remission (CR), CR with partial hematologic recovery (CRh), or CR with incomplete hematologic recovery (CRi). Patients with a mutation in FLT3, IDH1 or IDH2 must have failed or been intolerant of a corresponding Food and Drug Administration (FDA) approved FLT3, IDH1 or IDH2 inhibitor before enrolling on study. The initial diagnosis of AML is defined by the ELN 2022 criteria, and therefore patients with either AML (peripheral blood or bone marrow blasts ≥ 20% or blasts ≥ 10% with recurrent genetic abnormalities) or MDS/AML (peripheral blood or bone marrow blasts 10-19%) are eligible
- Refractory AML is defined as failure to achieve a CR, CRh, or CRi after one of the following regimens: (i) ≥ 2 cycles of intensive induction chemotherapy with a cytarabine containing regimen (e.g., 7+3, mitoxantrone, etoposide, cytarabine [MEC], high-dose cytarabine [HIDAC], reinduction chemotherapy such as 5 + 2, etc.) or, (ii) ≥ 2 cycles of hypomethylating agent (HMA)/venetoclax or low-dose cytarabine (LDAC)/glasdegib or, (iii) ≥ 4 cycles of HMA monotherapy. The initial diagnosis of AML is defined by the ELN 2022 criteria, and therefore patients with either AML (peripheral blood or bone marrow blasts ≥ 20% or blasts ≥ 10% with recurrent genetic abnormalities) or MDS/AML (peripheral blood or bone marrow blasts 10-19%) are eligible
- Patients with MDS/AML (blasts 10-19%) who progress to AML (blasts ≥ 20%) after treatment will be considered relapsed or refractory MDS/AML, and not as newly-diagnosed AML (i.e. the patients' treatment history for eligibility purposes does not reset)
- Relapsed MDS is defined as: (i) Intermediate, high, or very high-risk disease by International Prognostic Scoring System-Revised (IPSS-R) and, (ii) Any relapse after achieving any 2023 IWG MDS defined response
- Refractory MDS is defined as: (i) Intermediate, high, or very high-risk disease by IPSS-R and > 5% blasts in the bone marrow or peripheral blood, (ii) Failure to achieve a response (as per IWG 2006 criteria) after ≥ 4 cycles of HMA monotherapy, or (iii) ≥ 2 cycles of HMA + venetoclax
In Cohort III, patients must have prior untreated high-risk MDS
- MDS with > 5% blasts in the bone marrow or peripheral blood AND
- IPSS-R high or very high-risk disease OR
- Molecular International Prognostic Scoring System (IPSS-M) high or very high-risk disease
- No more than one single prior cycle of DNMTi therapy
- Prior use of erythropoiesis stimulating agents (ESA), thrombopoietin agonists, lenalidomide, and luspatercept are allowed
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of SM08502 (cirtuvivint) in combination with ASTX727 in patients < 18 years of age, children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin; in that case a cut off of ≤ 4 × institutional ULN will be used)
Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x institutional ULN (unless considered due to organ involvement by the patient's myeloid malignancy; in that case a cut off of ≤ 5 x institutional ULN will be used)
Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73m^2
If female, patient must be either:
- Postmenopausal (surgically sterile or age > 55 years with no menses for 12 or more months without an alternative medical cause or age equal to 55 or less with no menses for 12 or more months without an alternative medical cause and a follicle stimulating hormone [FSH] level > 40 IU/L); or
- Of children bearing potential. These patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Patient must agree to have a negative urine or serum beta-human chorionic gonadotropin (HCG) test result during screening and repeated within 7 days prior to study drug (local labs are allowed) to be eligible
The effects of SM08502 (cirtuvivint) and ASTX727 on the developing human fetus are unknown. For this reason, and because these agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and during the treatment therapy. Women of childbearing age should agree to use adequate contraception for 7 months after completion of SM08502 (cirtuvivint) administration. For ASTX727, adequate contraception must continue for at least 6 months after last dose of ASTX727. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of the study and at least 4 months after the last dose of SM08502 (cirtuvivint) and 3 months after last dose of ASTX727. Women who are lactating must refrain from breastfeed during the study and at least for two weeks after last dose of ASTX727
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia or abnormal blood counts
Patients who are receiving any other investigational agents
Systemic anti-leukemic or other antineoplastic therapy within 14 days of first day of study treatment. Hydroxyurea may be continued through cycle 1 of treatment. Hydroxyurea is discouraged in subsequent cycles and should be discussed beforehand with principal investigator. If on venetoclax, then a wash-out period of at least five times the half-life of venetoclax is required. Exceptions: No wash-out required for intrathecal chemotherapy, hydroxyurea, cytarabine (Ara-C), or palliative radiation therapy to painful sites of leukemic disease. Patients are not allowed to receive concurrent therapy such as cytotoxic chemotherapy or radiation therapy for another cancer. Patients on hormonal adjuvant therapy for non-metastatic breast and prostate cancer or other minimally-myelosuppressive maintenance therapies for non-metastatic cancer may be eligible at the discretion of the study principal investigator (PI)
Patient is receiving known inhibitors or activators of flavin-containing monooxygenases (FMO1 or FMO3), and these cannot be stopped at least 5 days prior to SM08502 (cirtuvivint) treatment start. Known inhibitors of FOMO are chlorpromazine and imipramine
Patient is receiving strong inhibitors or strong inducers of CYP3A4/5 and these cannot be stopped at least 5 days prior to SM08502 (cirtuvivint) treatment start
- Strong inhibitors include grapefruit juice or grapefruit/grapefruit related citrus fruits (e.g., Seville oranges, pomelos), ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir, nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
- Strong inducers include phenobarbital, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin, clevidipine, and St. John's Wort. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance.
- While moderate inhibitors or moderate inducers of CYP3A4/5 are not an exclusion criteria for the trial, it is preferred that moderate inhibitors or moderate inducers of CYP3A4/5 be replaced prior to the first dose of SM08502 (cirtuvivint) and during study conduct where this is possible.
  - Moderate inhibitors include erythromycin, ciprofloxacin, verapamil, diltiazem, atazanavir, fluconazole, darunavir, delavirdine, amprenavir, fosamprenavir, aprepitant, imatinib, tofisopam, and cimetidine. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
  - Moderate inducers include bosentan, efavirenz, etravirine, modafinil, and nafcillin. Examples may be found at the FDA website. Refer to the prescribing information of concomitant medications if in doubt or consult the sponsor for guidance
History of allergic reactions attributed to compounds of similar chemical or biologic composition to SM08502 (cirtuvivint) or ASTX727
Chronic, active hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: patients with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface [HBs] antigen negative, anti-HBs antibody positive and anti-hepatitis B core [HBc] antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate. Patients who had prior HCV that has been definitively treated with negative HCV viral load prior to study initiation and no evidence of cirrhosis, are allowed to participate. If there is no known history of HBV infection no HBV studies need to be obtained. If there is no known history of HCV infection, no HCV studies need to be obtained
Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
Pregnant and lactating women are excluded from this study because SM08502 (cirtuvivint) is a small molecule inhibitor of CLK DYRK with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SM08502 (cirtuvivint), breastfeeding should be discontinued if the mother is treated with SM08502 (cirtuvivint). These potential risks may also apply to other agents used in this study
Patients with acute promyelocytic leukemia
Subject has symptomatic central nervous system (CNS) involvement with AML
Patient has immediate life-threatening, severe complications of their myeloid malignancy such as uncontrolled bleeding and/or uncontrolled infection
Patient has significant active cardiac disease within 6 months prior to the start of study treatment, including uncontrolled New York Heart Association (NYHA) class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke
Left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 30 days prior to the start of study treatment
Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. Patient needs to be able to swallow pills
Patient has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
Subject has prolonged corrected QC (QTc) interval (Fridericia's correction [QTcF]) ≥ 480 ms or known family history of long QT interval syndrome at screening

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: 순차적 할당
마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔 참가자 그룹 / 팔 시험 프로토콜에 따라 특정 중재/치료를 받거나 중재를 받지 않는 임상 시험 참가자 그룹 또는 하위 그룹입니다.	개입 / 치료 개입 / 치료 임상 연구의 초점이 되는 프로세스 또는 작업입니다. 개입에는 약물, 의료 기기, 절차, 백신 및 조사 중이거나 이미 사용 가능한 기타 제품이 포함됩니다. 개입에는 교육이나 식이요법 및 운동 수정과 같은 비침습적 접근법도 포함될 수 있습니다.
실험적: Cohort I (cirtuvivint) Patients receive cirtuvivint PO QD on days 1-5, 8-12, 15-19, and 22-26 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.	절차: Biospecimen Collection Undergo blood sample collection 다른 이름들: 생물학적 샘플 수집 생체 표본 수집 표본 수집 샘플 수집 절차: Echocardiography Test Undergo ECHO 다른 이름들: 심초음파 EC 절차: Multigated Acquisition Scan Undergo MUGA 다른 이름들: 혈액 풀 스캔 평형 방사성핵종 혈관조영술 게이티드 혈액 풀 이미징 무가 방사성핵종 뇌실조영술 RNVG SYMA 스캐닝 동기화된 다중 게이트 수집 스캐닝 무가 스캔 다중 게이트 획득 스캔 방사성핵종 뇌실도 스캔 게이트 하트 풀 스캔 RNV 스캔 절차: Bone Marrow Aspiration Undergo bone marrow aspiration 의약품: Cirtuvivint Given PO 다른 이름들: SM 08502 SM-08502 SM08502 Wnt 신호 전달 경로 억제제 SM08502
실험적: Cohort II (cirtuvivint) Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.	절차: Biospecimen Collection Undergo blood sample collection 다른 이름들: 생물학적 샘플 수집 생체 표본 수집 표본 수집 샘플 수집 절차: Echocardiography Test Undergo ECHO 다른 이름들: 심초음파 EC 절차: Multigated Acquisition Scan Undergo MUGA 다른 이름들: 혈액 풀 스캔 평형 방사성핵종 혈관조영술 게이티드 혈액 풀 이미징 무가 방사성핵종 뇌실조영술 RNVG SYMA 스캐닝 동기화된 다중 게이트 수집 스캐닝 무가 스캔 다중 게이트 획득 스캔 방사성핵종 뇌실도 스캔 게이트 하트 풀 스캔 RNV 스캔 절차: Bone Marrow Aspiration Undergo bone marrow aspiration 의약품: Cirtuvivint Given PO 다른 이름들: SM 08502 SM-08502 SM08502 Wnt 신호 전달 경로 억제제 SM08502
실험적: Cohort III (cirtuvivint, ASTX727) Patients receive cirtuvivint PO QD on days 1, 4, 8, 11, 15, 18, 22, and 25 and ASTX727 PO QD on days 1-5 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA at screening. In addition, patients undergo blood sample collection and bone marrow aspiration at screening and on study.	절차: Biospecimen Collection Undergo blood sample collection 다른 이름들: 생물학적 샘플 수집 생체 표본 수집 표본 수집 샘플 수집 절차: Echocardiography Test Undergo ECHO 다른 이름들: 심초음파 EC 절차: Multigated Acquisition Scan Undergo MUGA 다른 이름들: 혈액 풀 스캔 평형 방사성핵종 혈관조영술 게이티드 혈액 풀 이미징 무가 방사성핵종 뇌실조영술 RNVG SYMA 스캐닝 동기화된 다중 게이트 수집 스캐닝 무가 스캔 다중 게이트 획득 스캔 방사성핵종 뇌실도 스캔 게이트 하트 풀 스캔 RNV 스캔 절차: Bone Marrow Aspiration Undergo bone marrow aspiration 의약품: Decitabine and Cedazuridine Given PO 다른 이름들: ASTX727 CDA 억제제 E7727/데시타빈 조합제 ASTX727 세다주리딘/데시타빈 조합제 ASTX727 세다주리딘/데시타빈 정제 인코비 C-DEC 12-C ASTX 727 ASTX-727 이나코비 의약품: Cirtuvivint Given PO 다른 이름들: SM 08502 SM-08502 SM08502 Wnt 신호 전달 경로 억제제 SM08502

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주요 결과 측정

결과 측정	측정값 설명	기간
Maximum tolerated dose (MTD) 기간: Up to day 28	The MTD of cirtuvivint as monotherapy in relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R myelodysplastic syndrome (MDS) (Cohort I and II) and in combination with ASTX727 in frontline MDS (Cohort III). MTD will be defined as the highest dose level at which 0/6 or 1/6 subjects experience a dose-limiting toxicity.	Up to day 28
Recommended phase 2 dose (RP2D) 기간: Up to 3 years	The RP2D will be based on the MTD in both Cohort I and II as well as pharmacokinetic, pharmacodynamic and response data from Cohort I and II.	Up to 3 years

2차 결과 측정

결과 측정	측정값 설명	기간
Incidence of adverse events (AEs) 기간: Up to 30 days after last dose of study treatment	AEs will be graded using Common Terminology Criteria for Adverse Events version 5.0 and described by frequency, duration, and severity of treatment-emergent, treatment-related, and serious AEs. All reported toxicities, regardless of attribution, will be summarized by toxicity type and maximum grade, and sorted by number of patients experiencing the toxicity for each dosing cohort and overall.	Up to 30 days after last dose of study treatment
Clinical response 기간: Up to 5 years after end of treatment	Clinical response will be assessed based on the 2022 European LeukemiaNet criteria for AML and the 2023 International Working Group criteria for MDS. Clinical response will be described using descriptive statistics. Point estimates and exact binomial 95% confidence intervals (CIs) will be provided for binary endpoints such as response rate in participants treated at MTD.	Up to 5 years after end of treatment
Event-free survival (EFS) 기간: Up to 1 year	The Kaplan-Meier method will be used to estimated EFS with its 95% CI.	Up to 1 year
Overall survival (OS) 기간: Up to 1 year	The Kaplan-Meier method will be used to estimated OS with its 95% CI.	Up to 1 year

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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

National Cancer Institute (NCI)

수사관

수석 연구원: Evan C Chen, Dana-Farber - Harvard Cancer Center LAO

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

Maron MI, Abdel-Wahab O. Outstanding Questions to Understand and Target Splicing Factor-Mutant Blood Cancers. Blood Cancer Discov. 2026 May 5;7(3):348-352. doi: 10.1158/2643-3230.BCD-26-0047.

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)

2025년 8월 15일

기본 완료 (추정된)

2028년 6월 1일

연구 완료 (추정된)

2028년 6월 1일

연구 등록 날짜

최초 제출

2024년 6월 29일

QC 기준을 충족하는 최초 제출

2024년 6월 29일

처음 게시됨 (실제)

2024년 7월 3일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 11월 3일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 10월 31일

마지막으로 확인됨

2026년 10월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

NCI-2024-05326
UM1CA186709 (미국 NIH 보조금/계약)
10674 (기타 식별자: CTEP)
NCI-2024-05326 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
10674 (기타 식별자: Dana-Farber - Harvard Cancer Center LAO)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

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. .

급성 골수성 백혈병 및 골수이형성 증후군 환자의 결과를 개선하기 위해 항암제인 Cirtuvivint 및 ASTX727 및 ASTX727과 Venetoclax의 병용 테스트

골수이형성증후군(MDS) 및 급성 골수성 백혈병(AML) 환자를 대상으로 단일요법 및 ASTX727 및 ASTX727 + 베네토클락스와의 병용 요법으로 서투비빈트의 안전성을 평가하는 1상 연구

연구 개요

상태

정황

개입 / 치료

상세 설명

연구 유형

등록 (추정된)

단계

연락처 및 위치

연구 장소

참여기준

자격 기준

공부할 수 있는 나이

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디자인 세부사항

팔의 수

무기와 개입

참가자 그룹 / 팔

개입 / 치료

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정

측정값 설명

기간

2차 결과 측정

결과 측정

측정값 설명

기간

공동 작업자 및 조사자

스폰서

수사관

간행물 및 유용한 링크

일반 간행물

연구 기록 날짜

연구 주요 날짜

연구 시작 (실제)

기본 완료 (추정된)

연구 완료 (추정된)

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

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

IPD 계획 설명

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

미국 FDA 규제 기기 제품 연구

미국에서 제조되어 미국에서 수출되는 제품