ACTIVE_NOT_RECRUITING

Entrectinib in Combination With ASTX727 for the Treatment of Relapsed/Refractory TP53 Mutated Acute Myeloid Leukemia

Conditions

Acute Myeloid Leukemia Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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)

Quick Facts

Study Start:2022-10-28

Study Completion:2026-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05396859

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Must be able to understand and willing to sign an informed consent document. * Participants aged 18 years or older. * Morphologically documented AML in patients with relapsed/refractory disease, defined as having \>= 20% blasts in bone marrow or peripheral blood. * Documented TP53 mutation as seen on standard diagnostics in AML. * Aspartate aminotransferase (AST) \< 3 × upper limit of normal (ULN). * Alanine aminotransferase (ALT) \< 3 × ULN. * Total bilirubin \< 1.5 × ULN (except for patients with known Gilbert's syndrome). * Adequate renal function as defined by calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min OR serum creatinine \< 1.5 × ULN. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2. * Must be able to take oral medication. * Individuals of childbearing potential (IOCBP) must agree to use highly-effective method(s) of contraception during the study and six months after the last dose of study drugs. IOCBP must have a negative pregnancy test prior to study enrollment. * Sperm producing individuals must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study drugs. * Participants must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of their cancer.	* Isolated myeloid sarcoma (patients must have blood or marrow involvement with AML to enter the study). * Acute promyelocytic leukemia (M3). * Active central nervous system (CNS) involvement by AML. * Clinical signs/symptoms of leukostasis which has failed urgent therapy of at least 3 days duration, which may have included hydroxyurea or leukapheresis. * Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection. * Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis. * 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). * Prior entrectinib for other malignancies (prior decitabine therapy will not be excluded). * Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up. * Patients who are otherwise felt unable to comply with the protocol, in the opinion of the investigator. * Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial. * Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic (New York Heart Association \[NYHA\] class III or IV) congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction at presentation of AML, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled. * Patients with uncontrolled infection shall not be enrolled until infection is treated and controlled. * Participants with prior documented history of malabsorption syndrome (e.g., short gut syndrome) that might limit the bioavailability of study medications will be excluded.

Inclusion Criteria

Exclusion Criteria

* Must be able to understand and willing to sign an informed consent document.
* Participants aged 18 years or older.
* Morphologically documented AML in patients with relapsed/refractory disease, defined as having \>= 20% blasts in bone marrow or peripheral blood.
* Documented TP53 mutation as seen on standard diagnostics in AML.
* Aspartate aminotransferase (AST) \< 3 × upper limit of normal (ULN).
* Alanine aminotransferase (ALT) \< 3 × ULN.
* Total bilirubin \< 1.5 × ULN (except for patients with known Gilbert's syndrome).
* Adequate renal function as defined by calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min OR serum creatinine \< 1.5 × ULN.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2.
* Must be able to take oral medication.
* Individuals of childbearing potential (IOCBP) must agree to use highly-effective method(s) of contraception during the study and six months after the last dose of study drugs. IOCBP must have a negative pregnancy test prior to study enrollment.
* Sperm producing individuals must agree to use an adequate method of contraception starting with the first dose of study therapy through 3 months after the last dose of study drugs.
* Participants must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of their cancer.

* Isolated myeloid sarcoma (patients must have blood or marrow involvement with AML to enter the study).
* Acute promyelocytic leukemia (M3).
* Active central nervous system (CNS) involvement by AML.
* Clinical signs/symptoms of leukostasis which has failed urgent therapy of at least 3 days duration, which may have included hydroxyurea or leukapheresis.
* Known active human immunodeficiency virus (HIV), active hepatitis B or active hepatitis C infection.
* Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis.
* 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).
* Prior entrectinib for other malignancies (prior decitabine therapy will not be excluded).
* Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up.
* Patients who are otherwise felt unable to comply with the protocol, in the opinion of the investigator.
* Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial.
* Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic (New York Heart Association \[NYHA\] class III or IV) congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction at presentation of AML, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled.
* Patients with uncontrolled infection shall not be enrolled until infection is treated and controlled.
* Participants with prior documented history of malabsorption syndrome (e.g., short gut syndrome) that might limit the bioavailability of study medications will be excluded.

Contacts and Locations

Principal Investigator

Ronan T Swords, M.D.

PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Study Locations (Sites)

OHSU Knight Cancer Institute

Portland, Oregon, 97239

United States

Collaborators and Investigators

Sponsor: OHSU Knight Cancer Institute

Ronan T Swords, M.D., PRINCIPAL_INVESTIGATOR, OHSU Knight Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-10-28

Study Completion Date2026-06-30

Study Record Updates

Study Start Date2022-10-28

Study Completion Date2026-06-30

Terms related to this study

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia