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Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia

ConditionsAcute Myeloid LeukemiaMyelodysplastic Syndrome/Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorOHSU Knight Cancer Institute

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Documented intermediate- or adverse-risk AML based on European Leukemia Network (ELN) 2022 criteria

Note: Cases of AML (MDS) overlap with 10-19% bone marrow (BM) or peripheral blood (PB) blasts will be considered

Disqualifiers

Prior allergic response to iadademstat (IADA), venetoclax, azacitidine, or any excipients in the formulations

Body weight < 50 kg

Investigational therapy within 5 half-lives or, if unknown, within 28 days prior to start of IADA

Treatment for AML within 14 days prior to start of IADA. Cytoreduction for patients with proliferative disease must meet the criteria listed in inclusion criteria

Trial design

Design model

Sequential

Treatments tested in this trial

  • Azacitidine

    Drug

    Given SC

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

  • Echocardiography Test

    Procedure/Surgery

    Undergo ECHO

  • Iadademstat

    Drug

    Given PO

  • Multigated Acquisition Scan

    Procedure/Surgery

    Undergo MUGA

  • Questionnaire Administration

    Other intervention

    Ancillary study

  • Venetoclax

    Drug

    Given PO

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Treatment Dose Level -1 (iadademstat, azacitidine, venetoclax)Experimental treatment 8 interventions
Group B: Treatment Dose Level -2 (iadademstat, azacitidine, venetoclax)Experimental treatment 8 interventions
Group C: Treatment Dose Level 1 (iadademstat, azacitidine, venetoclax)Experimental treatment 8 interventions
Group D: Treatment Dose Level 2 (iadademstat, azacitidine, venetoclax)Experimental treatment 8 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose-limiting toxicities (DLTs) within specific iadademstat (IADA) dose levels

Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0).

Time frame
Start of IADA (cycle 1 of combination therapy) to end of cycle 1 (each cycle is 28 days)

Secondary outcomes

1

Percentage of efficacy-evaluable participants achieving composite complete remission (cCR)

Will be defined as achievement of complete remission (CR) or CR with partial hematologic recovery (CRh) or CR with incomplete blood count recovery (CRi) while on iadademstat+ azacitidine + venetoclax (IADA+AZA+VEN). Will be estimated for the efficacy-evaluable population with point estimates and exact binomial confidence intervals (CIs) as summary statistics. CRc rate will also be modeled with univariable logistic regressions to determine if any baseline patient or disease feature is correlated with clinical response as defined by these efficacy metrics.

Time frame
Start of IADA (cycle 1 of combination therapy) to end of investigational study treatment, average of 1 year
2

Percentage of efficacy-evaluable participants achieving an overall response (ORR)

Will be defined as the proportion of efficacy-evaluable participants who attain a PR or better (i.e., CR, CRh, CRi, morphologic leukemia-free state, or partial remission \[PR\]) while on IADA+AZA+VEN. Will be estimated for the efficacy-evaluable population with point estimates and exact binomial CIs as summary statistics. ORR will also be modeled with univariable logistic regressions to determine if any baseline patient or disease feature is correlated with clinical response as defined by these efficacy metrics.

Time frame
Start of IADA (cycle 1 of combination therapy) to end of investigational study treatment, average of 1 year
3

Incidence of treatment-emergent grade ≥ 3 adverse events (AEs)

Will be reported with descriptive statistics, at the overall patient level and by grade, attribution (i.e., a separate table for treatment-related AEs), and seriousness (i.e., separate tables for serious adverse events).

Time frame
Start of IADA (cycle 1 of combination therapy) to end of investigational study treatment, average of 1 year

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

OHSU Knight Cancer Institute

Lead sponsor

Oregon Health and Science University

Collaborator

Oryzon Genomics S.A.

Collaborator

Source ClinicalTrials.gov
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