This phase I trial studies the side effects and best dose of palbociclib when given alone and in combination with sorafenib, decitabine, dexamethasone or venetoclax in treating patients with leukemia that has come back (recurrent) or that does not respond to previous treatment (refractory). Palbociclib, sorafenib, decitabine, and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib alone and in combination with sorafenib, decitabine, dexamethasone or venetoclax may work better in treating patients with recurrent or refractory leukemia.
Additional locations may be listed on ClinicalTrials.gov for NCT03132454.
Locations matching your search criteria
United States
Texas
Houston
M D Anderson Cancer CenterStatus: Temporarily closed to accrual
Contact: Tapan M. Kadia
Phone: 713-563-3534
PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of various combinations with palbociclib in patients with relapsed and refractory leukemias.
SECONDARY OBJECTIVES:
I. To assess pharmacodynamic effects of palbociclib on the Cyclin-CDK-Rb axis in leukemic blasts of patients with relapsed/refractory (R/R) leukemias.
II. To explore the efficacy (complete response [CR], complete response without platelet recovery [CRp], complete remission without blood count recovery [CRi], partial response [PR], or clinical benefit [CB]) of palbociclib as a single-agent and in combinations in patients with R/R leukemias.
III. To explore biomarkers of response and resistance in patients with R/R leukemias treated with palbociclib.
IV. To assess the safety and tolerability of one cycle of single-agent palbociclib in patients with R/R leukemias.
OUTLINE: This is a dose-escalation study of sorafenib, decitabine, dexamethasone, and venetoclax. Patients are assigned to 1 of 4 arms.
ARM A: Patients receive palbociclib orally (PO) once daily (QD) on days 1-28. Patients also receive sorafenib PO QD or twice daily (BID) on days 1-28 beginning on cycle 2. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive palbociclib as in Arm I. Beginning cycle 2, patients receive palbociclib PO QD on days 1-7 and decitabine intravenously (IV) QD over 1 hour on days 8-17 of cycle 2 and days 8-12 of cycles 3-8. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive palbociclib as in Arm I. Patients also receive dexamethasone PO QD or IV over 15-30 minutes on days 1-4 and 15-18 beginning on cycle 2. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
ARM D: Patients receive palbociclib PO QD on days 1-28, and venetoclax PO QD on days 1-21. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorTapan M. Kadia
