A Phase Ib Investigation of the LSD1 Inhibitor Iadademstat (ORY-1001) in Combination With Azacitidine and Venetoclax in Newly Diagnosed AML
OHSU Knight Cancer Institute
Summary
This phase I trial tests the safety, side effects, and best dose of iadademstat when given together with azacitidine and venetoclax in treating patients with newly diagnosed acute myeloid leukemia (AML). Iadademstat inhibits the LSD1 protein and may lead to inhibition of cell growth in LSD1-overexpressing cancer cells. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 iadademstat with azacitidine and venetoclax may be safe, tolerable and/or effective in treating patients with newly diagnosed AML who cannot undergo intensive chemotherapy.
Description
PRIMARY OBJECTIVE: I. Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of iadademstat (IADA) when administered as part of the investigational combination (i.e., iadademstat + azacitidine + venetoclax \[IADA+AZA+VEN\]). SECONDARY OBJECTIVES: I. Assess the preliminary efficacy of the investigational regimen based on disease remission. II. Assess the preliminary efficacy of the investigational regimen based on clinical response. III. Assess the safety of the investigational regimen. EXPLORATORY OBJECTIVES: I. Assess survival in the absence of treatment fail…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients at least 18 years of age will be considered for inclusion without bias against gender identity, race, or ethnicity * Ability to comprehend the investigational nature of the study and provide written informed consent * Patients with previously untreated, morphologically documented AML based on World Health Organization (WHO) 2008 definitions who are ineligible for standard of care (SOC) intensive chemotherapy induction and also meet the following criteria: * Documented intermediate- or adverse-risk AML based on European Leukemia Network (ELN) 2022 criteria *…
Interventions
- DrugAzacitidine
Given SC
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- ProcedureEchocardiography Test
Undergo ECHO
- DrugIadademstat
Given PO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- OtherQuestionnaire Administration
Ancillary study
Location
- OHSU Knight Cancer InstitutePortland, Oregon