Palbociclib and Tazemetostat in Combination With CPX-351 for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

This phase I trial tests the safety, side effects, and best dose of palbociclib and tazemetostat in combination with CPX-351 in treating patients with acute myeloid leukemia (AML) that has come back (relapsed) or does not respond to treatment (refractory). CPX-351 is a combination of the chemotherapy drugs, daunorubicin and cytarabine, which is the standard of care for AML. Chemotherapy drugs 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. Palbociclib and tazemetostat are enzyme inhibitor drugs that are approved for treating certain cancers but not AML. These drugs may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 chemotherapy with enzyme inhibitors palbociclib and tazemetostat may kill more cancer cells.

Inclusion Criteria:Provide signed and dated informed consent formWilling to comply with all study procedures and be available for the duration of the studyMale or female >= 18 years of ageHistologically confirmed acute myeloid leukemia (non-M3) relapsed from or refractory to at least 1 prior line of therapy. Bone marrow aspirate and biopsy within 28 days of screening is acceptable. If no prior bone marrow biopsy is available, bone marrow biopsy must be performed during screening unless:* If the subject has >= 20% myeloblasts present in the peripheral blood, a bone marrow biopsy is not necessary to meet this criterionTreatment with a prior investigational agent is acceptable so long as it has not been administered within 2 weeks of enrollment and any prior adverse effects have resolved to grade 1 or less with the exception of alopeciaEastern Cooperative Oncology Group (ECOG) performance status of 2 or lessLife expectancy of at least 4 weeksMust be able to consume oral medicationSubjects must have recovered from the toxic effect of any prior therapy to =< grade 1 (except alopecia)Creatine clearance (CrCL) >= 45Total bilirubin < 2 x upper limit of normal (ULN)Female subjects of childbearing age must have a negative pregnancy testExclusion Criteria:Subjects with acute promyelocytic leukemiaSubjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissibleSubjects whose participation would result in a total cumulative dose of daunorubicin greater than 550 mg/m^2 or greater than 450 mg/m^2 if they previously received mediastinal radiationSubjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptomsSubjects must not be receiving growth factors (except erythropoietin)Subjects with currently active second malignancy with the exception of nonmelanoma skin cancer, carcinoma in situ of the cervix, resected prostate cancer with Gleason score =< 6Subjects with unstable cardiac disease or uncontrolled arrhythmiaSubjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapySubjects who are pregnant or breastfeedingSubjects with known allergic reactions to components of the study product(s)Anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study