Active — Not RecruitingPhase 1

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

United States13 participantsStarted 2022-10-28

Plain-language 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.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion 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. Exclusion Criteria: * Isolated myeloid sarcoma (patients must h…

What they're measuring

Incidence of dose limiting toxicities (DLTs)

Timeframe: From first dose of study drug (day 1 of cycle 0) to end of cycle 1 (each cycle = 28 days)

Trial details

NCT IDNCT05396859

SponsorOHSU Knight Cancer Institute

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-06-10