Testing the Anti-cancer Drug, Cirtuvivint, and Its Combination With ASTX727 and ASTX727 With Venetoclax to Improve Outcomes in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes
NCT Number: NCT06484062
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Acute Myeloid Leukemia|Myelodysplastic Syndrome|Recurrent Acute Myeloid Leukemia|Recurrent Myelodysplastic Syndrome|Refractory Acute Myeloid Leukemia|Refractory Myelodysplastic Syndrome
Interventions: PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|PROCEDURE: Bone Marrow Biopsy|DRUG: Cirtuvivint|DRUG: Decitabine and Cedazuridine|PROCEDURE: Echocardiography|PROCEDURE: Multigated Acquisition Scan|DRUG: Venetoclax
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 48
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-13
Completion Date: 2027-01-01

Summary:
This phase I trial tests the safety, side effects, and best dose of SM08502 (cirtuvivint) alone and in combination with ASTX727, as well as ASTX727 and venetoclax 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. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving cirtuvivint alone or in combination with ASTX727 or ASTX727 and venetoclax may be safe, tolerable, and/or effective in treating patients with AML and MDS.

Primary Outcome Measures: Maximum tolerated dose (MTD), The MTD of SM08502 (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) and in combination with ASTX727 + venetoclax in frontline AML (Cohort IV). MTD will be defined as the highest dose level at which 0/6 or 1/6 subjects experience a dose-limiting toxicity (DLT)., Up to day 28|Recommended phase 2 dose (RP2D), 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
Secondary Outcome Measures: Incidence of adverse events (AEs), 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, 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), The Kaplan-Meier method will be used to estimated EFS with its 95% CI., Up to 1 year|Overall survival (OS), The Kaplan-Meier method will be used to estimated OS with its 95% CI., Up to 1 year