A Two-Part Phase 1b Study Evaluating the Combination of Tazemetostat and CPX-351 (Part 1) and Palbociclib Pre-Treatment Followed by CPX-351 (Part 2) for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
This is a two-part phase Ib dose escalation study to evaluate the safety and preliminary efficacy of the combination of tazemetostat and CPX-351 (Part 1) and of pre-treatment with palbociclib followed by CPX-351 (Part 2) for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). Part 1 of the study will seek to establish the safety, tolerability, biological activity and recommended dose for further evaluation (RDFE) of tazemetostat in combination with standard-dose CPX-351. Part 2 of the study will seek to establish the safety, tolerability, biological activity RDFE of pre-treatment palbociclib prior CPX-351.
• Provide signed and dated informed consent form
• Willing to comply with all study procedures and be available for the duration of the study
• Male or female \>= 18 years of age
• Histologically 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 criterion
• Treatment 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 alopecia
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Life expectancy of at least 4 weeks
• Must be able to consume oral medication
• Subjects must have recovered from the toxic effect of any prior therapy to =\< grade 1 (except alopecia)
• Creatine clearance (CrCL) \>= 45
• Total bilirubin \< 2 x upper limit of normal (ULN)
• Female subjects of childbearing age must have a negative pregnancy test