Ignite Creation Date:
2025-12-24 @ 2:50 PM
Ignite Modification Date:
2026-01-09 @ 3:46 PM
Study NCT ID:
NCT05396859
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-17
First Post:
2022-04-20
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia
Sponsor:
OHSU Knight Cancer Institute
Organization:
Study Overview
Official Title:
A Phase I Study of Entrectinib in Combination With ASTX727 (35 mg Decitabine and 100 mg Cedazuridine) in Patients With Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia (AML)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-10
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 the safety, side effects, and best dose of entrectinib when given with ASTX727 in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or that does not respond to treatment (refractory) and has a genetic change (mutation) in the TP53 gene. ASTX727 is a combination of cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Entrectinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells. Giving ASTX727 and entrectinib together may kill more tumor cells in patients with AML.
Detailed Description:
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) of decitabine and cedazuridine (ASTX727) combined with entrectinib in relapsed/refractory (R/R) AML patients with TP53 mutations.
SECONDARY OBJECTIVE:
I. To assess overall safety and preliminary anti-AML activity of combined ASTX727 and entrectinib regimen.
EXPLORATORY OBJECTIVE:
I. To assess the potential pharmacodynamic changes observed with treatment consisting of entrectinib alone and in combination with decitabine.
OUTLINE: This is a dose-escalation study of entrectinib.
Patients receive entrectinib orally (PO) once daily (QD) on days 1-28 and ASTX727 PO QD on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.
I. To determine the maximum tolerated dose (MTD) of decitabine and cedazuridine (ASTX727) combined with entrectinib in relapsed/refractory (R/R) AML patients with TP53 mutations.
SECONDARY OBJECTIVE:
I. To assess overall safety and preliminary anti-AML activity of combined ASTX727 and entrectinib regimen.
EXPLORATORY OBJECTIVE:
I. To assess the potential pharmacodynamic changes observed with treatment consisting of entrectinib alone and in combination with decitabine.
OUTLINE: This is a dose-escalation study of entrectinib.
Patients receive entrectinib orally (PO) once daily (QD) on days 1-28 and ASTX727 PO QD on days 1-5. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 1 year.
Study Oversight
Has Oversight DMC:
True
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?: