A Phase I and Pharmacodynamic Trial of Timed Sequential Administration of the Cyclin Dependent Kinase 4/6 Inhibitor PD 0332991 Followed by Cytarabine Plus Mitoxantrone for Adults With Relapsed and Refractory Acute Leukemias and High-Risk Myelodysplasias

Date de début de l'étude : 1 septembre 2012

Inclusion Criteria: Adults age ≥ 18 years Multilineage bone marrow failure Serum creatinine ≤ 2.0 mg/dl Hepatic enzymes (AST, ALT) ≤ 3x upper limit of normal (ULN) Bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's disease, hemolysis or leukemic infiltration Left ventricular ejection fraction ≥ 45% QTc ≤ 470 msec RB expression is required for the action of PD 0332991. Because rb deletions and mutations are rare in acute leukemias and MDS, screening for RB expression will not be required before enrollment. Pretreatment biopsies will be stored and analyzed for RB expression if needed subsequently. Exclusion Criteria: • No more than 5 cytotoxic regimens Previous allogeneic or autologous stem cell transplantation permitted ≥ 3 weeks delay from prior cytotoxic chemotherapy or radiation therapy ≥ 2 week delay from prior biologic therapies including hematopoietic growth factors and vidaza or decitabine If using Hydroxyurea, steroids, tyrosine kinase/src kinase inhibitors, arsenic, interferon for count control, must be off therapy for ≥ 48 hours prior to beginning PD 0332991 No concomitant use of potent CYP450 3A4 inhibitors (e.g. triazole antifungal agents) or inducers (e.g. omperazole, dilantin, dexamethasone) within 7 days prior to beginning PD 0332991