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
Acute promyelocytic leukemia (or M3 AML)
Patients known to have core binding factor AML (defined as presence of t(8;21), inv(16), or other cytogenetically equivalent abnormalities)
Patients known to have inactivating mutations of TP53 or evidence of an absence of p53 protein activity as indicated by a monosomal karyotype. Monosomal karyotype will be defined as two or more monosomies (loss of an entire chromosome or the entire long arm of a chromosome [such as 7q-]) or a single monosomy in the setting of a complex karyotype. Patients with a complex karyotype without a monosomy are eligible to enroll
Patients that the treating physician does not feel are able to tolerate intensive chemotherapy
Single group
Liposome-encapsulated Daunorubicin-Cytarabine
DrugGiven IV
Incidence of adverse events
Will be measured by the time to count recovery, incidence of symptomatic cardiac dysfunction, incidence of hepatic or renal toxicity, incidence of severe hemorrhage, and incidence of severe infection. Will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 4, and frequency counts will be tabulated with a focus on severe (grade 3+) adverse events and toxicities that are deemed at least possibly related to study treatment. The incidence of specific toxicities will be calculated as the proportion of patients experience these toxicities over all patients who receive any study drug.
Calculation rate of complete response (CR) and complete response with incomplete hematologic recovery (CRi)
CR and CRi rate will be defined as the proportion of patients who achieve CR or CRi over all evaluable patients. The rates will be provided with 95% binomial confidence intervals.
Progression-free survival
Will be calculated by the method of Kaplan-Meier, with the 2-year estimate provided with 95% confidence interval.
Overall survival
Will be calculated by the method of Kaplan-Meier, with the 2-year estimate provided with 95% confidence interval.
Measurement of blast cell cycle fraction
Will be exploratory in nature with graphical methods and descriptive statistics provided to gather preliminary information. Nonparametric method such Mann-Whitney U test will be utilized to compare pre and post-treatment data, and box plot or spaghetti plot will be presented to help visualize the trend of change.
Relative clearance immunophenotypically abnormal blast and stem cells
Will be exploratory in nature with graphical methods and descriptive statistics provided to gather preliminary information. Nonparametric method such Mann-Whitney U test will be utilized to compare pre and post-treatment data, and box plot or spaghetti plot will be presented to help visualize the trend of change.
Efficacy of blast cell and leukemia stem/repopulating cell (LSC) elimination
Will compare the efficacy of blast cell and LSC elimination in patients receiving Vyxeos re-induction compared to similar blast cells and LSCs in patients receiving standard 7+3 or 5+2 re-induction. Will be exploratory in nature with graphical methods and descriptive statistics provided to gather preliminary information. Nonparametric method such Mann-Whitney U test will be utilized to compare pre and post-treatment data, and box plot or spaghetti plot will be presented to help visualize the trend of change.
Number of patients proceeding to stem cell transplantation following Vyxeos treatment
Will be measured and is exploratory in nature. It will be analyzed with descriptive statistics to gather preliminary information and compared to historical controls.
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