NCT03132454

Palbociclib and Sorafenib, Decitabine, or Dexamethasone in Treating Patients With Recurrent or Refractory Leukemia

Phase I Study of Palbociclib Alone and in Combination in Patients With Relapsed and Refractory Leukemias

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 15 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of palbociclib when given alone and in combination with sorafenib, decitabine, or dexamethasone in treating patients with leukemia that has come back (recurrent) or that does not respond to previous treatment (refractory). Palbociclib, sorafenib, and decitabine 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, or dexamethasone may work better in treating patients with recurrent or refractory leukemia.

Detailed description

PRIMARY OBJECTIVES: 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 remission 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, and dexamethasone. Patients are assigned to 1 of 3 arms. ARM I: Patients receive palbociclib orally (PO) once daily (QD) on days 1-28. Patients also receive sorafenib PO QD 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 II: Patients receive palbociclib as in Arm I. Beginning cycle 2, patients receive palbociclib PO QC 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 III: 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. After completion of study treatment, patients are followed up periodically.

Conditions

• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Decitabine	Given IV
DRUG	Dexamethasone	Given IV or PO
DRUG	Palbociclib	Given PO
DRUG	Sorafenib	Given PO

Timeline

• Start date: 2017-07-25
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2017-04-27
• Last updated: 2026-04-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study