Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia
brief 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.
detailed 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 failure, hematologic relapse, or progressive disease.
II. Assess overall survival.
III. Assess duration of response, based on morphological assessments.
IV. Identify mechanisms of transcriptional reprogramming and cell death.
V. Identify predictive biomarkers of response to LSD1 inhibition.
VI. Assess participant quality of life using Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE).
OUTLINE: This is a dose-escalation study of iadademstat in combination with azacitidine and venetoclax.
Patients receive iadademstat orally (PO) once daily (QD) on days 1-5, 8-12, and 15-19. Patients also receive venetoclax PO QD days 1-21 or 1-28 and azacitidine subcutaneously (SC) QD days 1-7. Patients with complete remission (CR), CR with partial hematologic recovery (CRh), CR with incomplete blood count recovery, (CRi), or morphologic leukemia-free state (MLFS) after cycle 1 continue to receive IADA PO QD on days 1-5, 8-12, and 15-19, azacitidine SC QD days 1-7 and venetoclax PO QD days 1-21 or 1-28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening as clinically indicated on study. Patients under bone marrow biopsy throughout the trial. Additionally, patients undergo blood sample collection during screening and on the trial.
official title
A Phase Ib Investigation of the LSD1 Inhibitor Iadademstat (ORY-1001) in Combination With Azacitidine and Venetoclax in Newly Diagnosed AML