Tazemetostat and Palbociclib With CPX-351for R/R AML
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
Thomas Jefferson University
24 participants
Aug 28, 2023
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria13
- 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
Exclusion Criteria11
- Subjects with acute promyelocytic leukemia
- Subjects receiving any active chemotherapy agents (except hydroxyurea). Intrathecal methotrexate and cytarabine are permissible
- Subjects 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 radiation
- Subjects with evidence of active central nervous system (CNS) leukemia involvement. Lumbar puncture is not required for enrollment in the absence of neurologic symptoms
- Subjects 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 =\< 6
- Subjects with unstable cardiac disease or uncontrolled arrhythmia
- Subjects with other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate to receive high-intensity therapy
- Subjects who are pregnant or breastfeeding
- Subjects 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
Interventions
Given PO
Given IV
Undergo bone marrow aspiration and biopsy
Undergo blood sample collection
Given PO
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05627232