Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML
NCT Number: NCT06514261
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Acute Myeloid Leukemia
Interventions: DRUG: Azacitidine|PROCEDURE: Biospecimen Collection|PROCEDURE: Bone Marrow Aspiration|DRUG: Iadademstat|DRUG: Venetoclax
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 45
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-20
Completion Date: 2026-09-01

Summary:
This phase I trial tests safety, side effects and best dose of iadademstat with azacitidine and venetoclax for the treatment of patients with acute myeloid leukemia (AML) who have not receive treatment (treatment naive). Chemotherapy drugs, such as iadademstat and 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 and tolerable in treating patients with treatment naive AML.

Primary Outcome Measures: Incidence of dose limiting toxicity (DLT), DLT is defined as any of the following treatment emergent adverse events occurring in the first cycle that are related (possibly, probably, or definitely) to administration of the study agents. Will utilize National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for toxicity grading and reporting., Up to completion of cycle 1|Incidence of adverse events (AEs), Will utilize NCI-CTCAE v5.0 for AE grading and reporting., Up to completion of therapy
Secondary Outcome Measures: Objective response rate, The probability of achieving a complete remission (CR), CR with incomplete hematologic recovery (CRi), CR with partial hematologic recovery (CRh), will be estimated with exact 95% binomial confidence intervals., Up to 4 years|Morphologic leukemia free state, Up to 4 years|Minimal residual disease-negative composite complete remission (cCR), Will be estimated with exact 95% binomial confidence intervals., After completion of 2 cycles|Event free survival, Will be estimated by the Kaplan-Meier method, along with 95% confidence regions., From study enrollment to disease progression, treatment failure (failure to achieve CR or <5% bone marrow blasts) confirmed relapse or death, up to 4 years|Overall survival, Will be estimated by the Kaplan-Meier method, along with 95% confidence regions., Up to 4 years|Duration of response, Will be estimated by the Kaplan-Meier method, along with 95% confidence regions., Up to 4 years|Proportion of patients with high risk molecular and cyteogenetic markers, Will be estimated with exact 95% binomial confidence intervals and compared between baseline, during treatment, and at progression of disease., At baseline, during treatment, and at progression of disease, up to 4 years
Other Outcome Measures: MRD-negative cCR and molecular/cytogenetic risk group status, Rates of MRD-negative cCR will be tabulated descriptively across molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) subgroups. Will be estimated with exact 95% binomial confidence intervals., After cycles 1, 3 and 6|Percentage LSD1 target engagement by chemoprobe in peripheral blood mononuclear cells, Changes in %LSD1 target engagement will be compared between patients and between dose levels to confirm target engagement. Data between dose levels will be compared with a rank sum test and within patients with a signed rank test and/or mixed effects regression. Data between dose levels will be compared with a rank sum test and within patients with a signed rank test and/or mixed effects regression., Up to 4 years|BCL-2 mutations by next generations sequencing (NGS) in bone marrow (BM) of patients who initially respond and then progress, At baseline, during treatment, and at progression of disease, up to 4 years|BAX mutations by NGS in BM of patients who initially respond and then progress, At baseline, during treatment, and at progression of disease, up to 4 years|Mutations by NGS in relevant genes in BM of patients who initially respond and then progress, At baseline and at progression of disease, up to 4 years|Expression of MCL-1, BCL-XL and related proteins in PBMCs of patients who initially respond and then progress, At baseline, during treatment, and at progression of disease, up to 4 years|Venetoclax trough, Day 5, 8 and 12|Iadademstat through and derived pharmacokinetic parameters, Up to 4 years