← Back to Search

Cytidine Deaminase Inhibitor

Entrectinib + ASTX727 for Acute Myeloid Leukemia

Phase 1
Recruiting
Led By Ronan T Swords, M.D.
Research Sponsored by OHSU Knight Cancer Institute
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Adequate renal function as defined by calculated creatinine clearance (according to the Cockcroft-Gault equation) > 40 mL/min OR serum creatinine < 1.5 × ULN
Documented TP53 mutation as seen on standard diagnostics in AML
Must not have
Patients who have received an investigational agent (for any indication) within 5 half-lives of the agent or who have agent-related toxicity that has not resolved to grade 1 or less. If the half-life of an investigational agent is unknown, patients must wait 1 week after discontinuing it before receiving the first dose of study treatment. An investigational agent is one for which there is no approved indication by the United States (US) Food and Drug Administration (FDA)
Participants with prior documented history of malabsorption syndrome (e.g., short gut syndrome) that might limit the bioavailability of study medications will be excluded
Timeline
Screening 3 weeks
Treatment Varies
Follow Up from first dose of study drug up to 2 weeks after last dose of study drug, start of new cancer therapy, or transplant (whichever is first), assessed up to 6 months
Awards & highlights

Summary

This trial is testing the safety of a combination of drugs for patients with leukemia who have a specific genetic mutation. The combination of drugs may kill more cancer cells than either drug alone.

Who is the study for?
Adults with relapsed/refractory AML and a TP53 mutation can join this trial. They must understand the study, be able to take oral meds, have decent organ function, and use contraception. Excluded are those with certain leukemia types, active infections like HIV or hepatitis B/C, uncontrolled diseases, recent investigational drugs usage or conditions affecting drug absorption.Check my eligibility
What is being tested?
The trial is testing entrectinib combined with ASTX727 (cedazuridine plus decitabine) for safety and effectiveness in AML patients. Entrectinib blocks cancer cell growth signals; cedazuridine increases decitabine's availability which helps produce normal blood cells and kills abnormal ones.See study design
What are the potential side effects?
Potential side effects include reactions related to immune system activation such as inflammation of organs, infusion-related symptoms, fatigue from treatment burden on the body, digestive issues due to medication impact on gut health, possible blood disorders from bone marrow activity changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
My kidney function is within the required range.
Select...
My AML has a confirmed TP53 mutation.
Select...
My AML has returned or didn't respond to treatment, with at least 20% cancer cells in my blood or bone marrow.
Select...
I can take care of myself but might not be able to do heavy physical work.
Select...
I am 18 years old or older.
Select...
I can take medicine by mouth.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I haven't taken any experimental drugs recently or still have side effects from one.
Select...
I do not have a history of conditions like short gut syndrome that affect medication absorption.
Select...
I do not have any severe heart problems or other serious illnesses that are not under control.
Select...
I have a blood clotting disorder with active bleeding or signs of clotting.
Select...
I have been diagnosed with a specific type of leukemia called M3.
Select...
I have AML affecting my blood or bone marrow.
Select...
My acute myeloid leukemia has spread to my brain or spinal cord.
Select...
I do not have active HIV, hepatitis B, or hepatitis C.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~from first dose of study drug up to 2 weeks after last dose of study drug, start of new cancer therapy, or transplant (whichever is first), assessed up to 6 months
This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose of study drug up to 2 weeks after last dose of study drug, start of new cancer therapy, or transplant (whichever is first), assessed up to 6 months for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Incidence of dose limiting toxicities (DLTs)
Secondary outcome measures
Clinical benefit rate (CBR)
Composite complete remission (CCR) rate
Duration of response (DOR)
+5 more
Other outcome measures
Pyruvate Kinase
Genomic analysis
NTRK gene expression
+4 more

Trial Design

1Treatment groups
Experimental Treatment
Group I: Treatment (ASTX727, entrectinib)Experimental Treatment3 Interventions
Patients receive entrectinib PO 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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Entrectinib
FDA approved

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.
Mechanism Of Action
Side Effect Profile
Prior Approvals
Other Research
Common treatments for Acute Myelogenous Leukemia (AML) include hypomethylating agents, cytidine deaminase inhibitors, and kinase inhibitors. Hypomethylating agents like decitabine inhibit DNA methylation, reactivating tumor suppressor genes and inducing cancer cell death. Cytidine deaminase inhibitors, such as cedazuridine, prevent the breakdown of hypomethylating agents, enhancing their effectiveness. Kinase inhibitors like entrectinib block abnormal proteins that signal cancer cells to multiply, slowing or stopping cancer spread. These treatments are crucial for AML patients as they target the genetic and molecular abnormalities driving the disease, offering a more tailored and potentially effective approach.
Molecular targeting in acute myeloid leukemia.

Find a Location

Who is running the clinical trial?

OHSU Knight Cancer InstituteLead Sponsor
231 Previous Clinical Trials
2,088,478 Total Patients Enrolled
Genentech, Inc.Industry Sponsor
1,542 Previous Clinical Trials
568,065 Total Patients Enrolled
Taiho Oncology, Inc.Industry Sponsor
66 Previous Clinical Trials
11,532 Total Patients Enrolled

Media Library

Acute Myelogenous Leukemia Research Study Groups: Treatment (ASTX727, entrectinib)
~2 spots leftby Dec 2024
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top