Ignite Creation Date:
2025-12-24 @ 1:00 PM
Ignite Modification Date:
2026-01-25 @ 11:06 AM
Study NCT ID:
NCT06514261
Status:
RECRUITING
Last Update Posted:
2025-12-24
First Post:
2024-07-20
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase 1 Trial of Iadademstat in Combination With Venetoclax and Azacitidine in Patients With Treatment Naive AML
Status:
RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 received 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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine the recommended phase 2 dose (RP2D) and safety profile of iadademstat in combination with venetoclax and azacitidine.
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity, including evaluating the overall response rate (ORR), defined as complete remission (CR), CR with incomplete hematologic recovery (Cri), or CR with partial hematologic recovery (CRh).
II. To evaluate the measurable residual disease (MRD)-negative composite CR (cCR) rate after 1, 2, and 3 cycles using multiparameter flow cytometry (MFC) and evaluate event-free survival (EFS), overall survival (OS), and duration of response (DoR).
III. To determine if treatment will be associated with expansion of high risk molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) markers over time.
EXPLORATORY OBJECTIVES:
I. To determine the rate of MRD-negative cCR across molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) subgroups.
II. To document the effect of therapy on LSD1-target engagement.
III. To determine if secondary resistance (remission with therapy then relapse) in both arms is associated with:
IIIa. Acquisition of resistance mutations including BCL-2 and BAX; IIIb. Development or expansion of mutations that activate RAS/MAPK/FLT3 including NRAS, KRAS, PTPN11, NF1, and FLT3-ITD; IIIc. Over-expression of resistance proteins such as MCL-1 or BCL-XL. IV. To determine pharmacokinetics (PK) in the triplet therapy of iadademstat, azacitidine, and venetoclax.
V. To explore PK/pharmacodynamic (PD) relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat, azacitidine, and venetoclax.
VI. To evaluate the association between time to achieve an MRD-negative cCR and EFS, OS, and DoR.
OUTLINE: This is a dose-escalation study of iadademstat and venetoclax in combination with azacitidine.
INDUCTION: Patients receive iadademstat orally (PO) once daily (QD) on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study.
CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.
After completion of study treatment, patients are followed every 3-4 months for up to 2 years.
I. To determine the recommended phase 2 dose (RP2D) and safety profile of iadademstat in combination with venetoclax and azacitidine.
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity, including evaluating the overall response rate (ORR), defined as complete remission (CR), CR with incomplete hematologic recovery (Cri), or CR with partial hematologic recovery (CRh).
II. To evaluate the measurable residual disease (MRD)-negative composite CR (cCR) rate after 1, 2, and 3 cycles using multiparameter flow cytometry (MFC) and evaluate event-free survival (EFS), overall survival (OS), and duration of response (DoR).
III. To determine if treatment will be associated with expansion of high risk molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) markers over time.
EXPLORATORY OBJECTIVES:
I. To determine the rate of MRD-negative cCR across molecular (PTPN11, NRAS, KRAS, NF1, and TP53) and cytogenetic (complex karyotype) subgroups.
II. To document the effect of therapy on LSD1-target engagement.
III. To determine if secondary resistance (remission with therapy then relapse) in both arms is associated with:
IIIa. Acquisition of resistance mutations including BCL-2 and BAX; IIIb. Development or expansion of mutations that activate RAS/MAPK/FLT3 including NRAS, KRAS, PTPN11, NF1, and FLT3-ITD; IIIc. Over-expression of resistance proteins such as MCL-1 or BCL-XL. IV. To determine pharmacokinetics (PK) in the triplet therapy of iadademstat, azacitidine, and venetoclax.
V. To explore PK/pharmacodynamic (PD) relationship of iadademstat and venetoclax in patients who received the triplet therapy of iadademstat, azacitidine, and venetoclax.
VI. To evaluate the association between time to achieve an MRD-negative cCR and EFS, OS, and DoR.
OUTLINE: This is a dose-escalation study of iadademstat and venetoclax in combination with azacitidine.
INDUCTION: Patients receive iadademstat orally (PO) once daily (QD) on days 1-5, 8-12, and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-14 or 1-21 of each cycle, and azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo buccal swab collection on study.
CONSOLIDATION: Patients receive iadademstat PO QD on days 1-5, 8-12 and may also receive it on days 15-19 of each cycle, venetoclax PO QD on days 1-7 or 1-14 of each cycle, and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle or days 1-5 and 8-9 after cycle 1. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection and may undergo bone marrow aspiration throughout the study.
After completion of study treatment, patients are followed every 3-4 months for up to 2 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: