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Testen van het antikankermedicijn Cirtuvivint en de combinatie ervan met ASTX727 en ASTX727 met Venetoclax om de resultaten te verbeteren bij patiënten met acute myeloïde leukemie en myelodysplastische syndromen

31 oktober 2026 bijgewerkt door: National Cancer Institute (NCI)

Een fase I-studie ter evaluatie van de veiligheid van Cirtuvivint als monotherapie en in combinatie met ASTX727 en ASTX727 + Venetoclax bij patiënten met myelodysplastische syndromen (MDS) en acute myeloïde leukemie (AML)

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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Geschat)

54

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Sequentiële toewijzing
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Procedure: Biospecimen Collection

Undergo blood sample collection

Andere namen:
  • Biologische monsterverzameling
  • Biospecimen verzameld
  • Specimenverzameling
  • Monsterverzameling
Procedure: Echocardiography Test

Undergo ECHO

Andere namen:
  • Echocardiografie
  • EG
Procedure: Multigated Acquisition Scan

Undergo MUGA

Andere namen:
  • Blood Pool-scan
  • Equilibrium radionuclide angiografie
  • Gated Blood Pool-beeldvorming
  • MUGA
  • Radionuclide ventriculografie
  • RNVG
  • SYMA scannen
  • Gesynchroniseerde Multigated Acquisitie Scannen
  • MUGA-scan
  • Multi-Gated Acquisitie Scan
  • Radionuclide ventriculogram scan
  • Gated Heart Pool-scan
  • RNV-scan
Procedure: Bone Marrow Aspiration

Undergo bone marrow aspiration

Geneesmiddel: Cirtuvivint

Given PO

Andere namen:
  • SM 08502
  • SM-08502
  • SM08502
  • Wnt-signaleringsroute-remmer SM08502
Experimenteel: 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.
Procedure: Biospecimen Collection

Undergo blood sample collection

Andere namen:
  • Biologische monsterverzameling
  • Biospecimen verzameld
  • Specimenverzameling
  • Monsterverzameling
Procedure: Echocardiography Test

Undergo ECHO

Andere namen:
  • Echocardiografie
  • EG
Procedure: Multigated Acquisition Scan

Undergo MUGA

Andere namen:
  • Blood Pool-scan
  • Equilibrium radionuclide angiografie
  • Gated Blood Pool-beeldvorming
  • MUGA
  • Radionuclide ventriculografie
  • RNVG
  • SYMA scannen
  • Gesynchroniseerde Multigated Acquisitie Scannen
  • MUGA-scan
  • Multi-Gated Acquisitie Scan
  • Radionuclide ventriculogram scan
  • Gated Heart Pool-scan
  • RNV-scan
Procedure: Bone Marrow Aspiration

Undergo bone marrow aspiration

Geneesmiddel: Cirtuvivint

Given PO

Andere namen:
  • SM 08502
  • SM-08502
  • SM08502
  • Wnt-signaleringsroute-remmer SM08502
Experimenteel: 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.
Procedure: Biospecimen Collection

Undergo blood sample collection

Andere namen:
  • Biologische monsterverzameling
  • Biospecimen verzameld
  • Specimenverzameling
  • Monsterverzameling
Procedure: Echocardiography Test

Undergo ECHO

Andere namen:
  • Echocardiografie
  • EG
Procedure: Multigated Acquisition Scan

Undergo MUGA

Andere namen:
  • Blood Pool-scan
  • Equilibrium radionuclide angiografie
  • Gated Blood Pool-beeldvorming
  • MUGA
  • Radionuclide ventriculografie
  • RNVG
  • SYMA scannen
  • Gesynchroniseerde Multigated Acquisitie Scannen
  • MUGA-scan
  • Multi-Gated Acquisitie Scan
  • Radionuclide ventriculogram scan
  • Gated Heart Pool-scan
  • RNV-scan
Procedure: Bone Marrow Aspiration

Undergo bone marrow aspiration

Geneesmiddel: Decitabine and Cedazuridine

Given PO

Andere namen:
  • ASTX727
  • CDA-remmer E7727/decitabine combinatiemiddel ASTX727
  • Cedazuridine/Decitabine Combinatiemiddel ASTX727
  • Cedazuridine/Decitabine-tablet
  • Inqovi
  • C-DEC
  • DEC-C
  • ASTX 727
  • ASTX-727
  • Inaqovi
Geneesmiddel: Cirtuvivint

Given PO

Andere namen:
  • SM 08502
  • SM-08502
  • SM08502
  • Wnt-signaleringsroute-remmer SM08502

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Maximum tolerated dose (MTD)
Tijdsspanne: 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)
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of adverse events (AEs)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: Up to 1 year

The Kaplan-Meier method will be used to estimated OS with its 95% CI.
Up to 1 year

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Cancer Institute (NCI)

Onderzoekers

  • Hoofdonderzoeker: Evan C Chen, Dana-Farber - Harvard Cancer Center LAO

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

15 augustus 2025

Primaire voltooiing (Geschat)

1 juni 2028

Studie voltooiing (Geschat)

1 juni 2028

Studieregistratiedata

Eerst ingediend

29 juni 2024

Eerst ingediend dat voldeed aan de QC-criteria

29 juni 2024

Eerst geplaatst (Werkelijk)

3 juli 2024

Updates van studierecords

Laatste update geplaatst (Werkelijk)

3 november 2026

Laatste update ingediend die voldeed aan QC-criteria

31 oktober 2026

Laatst geverifieerd

1 oktober 2026

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • NCI-2024-05326
  • UM1CA186709 (Subsidie/contract van de Amerikaanse NIH)
  • 10674 (Andere identificatie: CTEP)
  • NCI-2024-05326 (Register-ID: CTRP (Clinical Trial Reporting Program))
  • 10674 (Andere identificatie: Dana-Farber - Harvard Cancer Center LAO)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren