A Phase I Study Evaluating the Safety of Cirtuvivint as Monotherapy and in Combination With ASTX727 in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)
National Cancer Institute (NCI)
Summary
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.
Description
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 (ci…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 AM…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- DrugCirtuvivint
Given PO
- DrugDecitabine and Cedazuridine
Given PO
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
Locations (21)
- Yale UniversityNew Haven, Connecticut
- Emory University Hospital/Winship Cancer InstituteAtlanta, Georgia
- University of Chicago Comprehensive Cancer CenterChicago, Illinois
- UC Comprehensive Cancer Center at Silver CrossNew Lenox, Illinois
- University of Chicago Medicine-Orland ParkOrland Park, Illinois
- UChicago Medicine Northwest IndianaCrown Point, Indiana