Open-Label Phase 2 Trial of Vyxeos in Patients With Intermediate and High-Risk Acute Myeloid Leukemia Who Have Failed an Initial Cycle of Standard Cytarabine and Daunorubicin Chemotherapy
This phase II trial studies the side effects and how well Vyxeos works in treating patients with intermediate and high-risk acute myeloid leukemia who have failed an initial cycle of standard cytarabine and daunorubicin chemotherapy. Vyxeos is a combination of both chemotherapy drugs cytarabine and daunorubicin contained in a liposome. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cytarabine and daunorubicin given together in liposomes may have fewer side effects and work better than cytarabine and daunorubicin given alone in patients with acute myeloid leukemia.
• Subject must be able to provide written informed consent
• Patients must have a diagnosis of acute myeloid leukemia
• Patients must have received standard induction chemotherapy (cytarabine 100-200mg/m2 by continuous infusion on days 1-7 and either daunorubicin 45-90mg/m2 or idarubicin 10-12mg/ m2 daily for 3 days during days 1-7) within the 14-33 days prior to starting trial treatment and have documented persistent disease (13-29 days from the start of 7+3 treatment). Patients who have received a 7+3 regimen utilizing gemtuzumab ozogamicin may enroll. Patients who received lower doses of the above agents due to appropriate adjustments for reduced renal or hepatic clearance may also enroll. Persistent disease will be defined as bone marrow cellularity of \>10-20% and bone marrow blast percentage of \>5-10% or clear evidence of immunophenotypically aberrant leukemia cells in the bone marrow. The final determination of persistent AML will be made by the treating physician, but must meet NCCN criteria for persistent disease1. Enrollment of patients with less than 20% cellularity or less than 10% blasts will require approval of the principal investigator. Patients who received concomitant treatment with another targeted therapy for AML that is FDA-approved for administration with 7+3 (e.g. midostaurin) may enroll and can continue to receive this treatment (according to the FDA-approved 7+3 re-induction dosing schedule) during Vyxeos treatment.
• Patients must be deemed by the treating physician to be unlikely to achieve complete response (CR) without further therapy
• Patients must be deemed by the treating physician to be able to tolerate intensive chemotherapy (similar to 7+3 chemotherapy)
• Normal left ventricular ejection fraction (\>= 50% by echocardiography or multi-gated acquisition radionuclide angiocardiography \[MUGA\]) and lifetime daunorubicin dose of less than 462mg/m\^2 (including recent course of 7+3), or equivalent doses of another anthracycline medications. (This is 550mg/m\^2 \[maximum lifetime dose\] minus 88mg/m\^2 \[planned dose of Vyxeos on study\].)
• Eastern Cooperative Oncology Group (ECOG) functional status of 0, 1, or 2
• Aspartate aminotransferase (AST) \< 5 x upper limit of normal (ULN) for the local laboratory
• Alanine aminotransferase (ALT) \< 5 x ULN for the local laboratory
• Total bilirubin \< 1.5 x ULN (except for patients with known Gilbert?s syndrome) for the local laboratory
• Calculated creatinine clearance (according to the Cockcroft-Gault equation) \> 40 mL/min OR serum creatinine \< 1.5 x the ULN for the local laboratory
• Female patients of childbearing potential must agree to use two forms of contraception from screening visit until 6 months following the last dose of study treatment. Female patients must have a documented negative pregnancy test
• Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use two forms of contraception from screening visit until 6 months after the last dose of study treatment. They must also refrain from sperm donation from screening visit until 6 months following the last dose of study treatment