Sertraline and Cytosine Arabinoside in Adults With Relapsed and Refractory AML

Inclusion Criteria:

Pathologically-confirmed diagnoses of relapsed AML: Patients with AML that have relapsed at least once or are primary induction failure will be eligible
Age ≥ 18 and ≤ 70 years
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
≥ 2 weeks off cytotoxic chemotherapy
≥ 2 weeks off radiation therapy
Off biologic therapies including hematopoietic growth factors ≥ 1 week
If using tyrosine kinase inhibitors (TKIs)/src inhibitors, other non-cytotoxics, or leukopheresis for blast count control, the patient must be off these therapies for > 24 hrs before starting sertraline. Hydroxyurea will be allowed with sertraline but should be stopped ≥24 hours before starting cytarabine.

Adequate organ function as defined below:

Renal function: Serum creatinine <2.0 mg/dL or creatinine clearance ≥ 50 mL/minute
Hepatic function: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Alkaline Phosphatase ≤ 5x Upper Limit normal (ULN), bilirubin ≤ 2.0 mg/dl, unless due to Gilbert's, hemolysis or leukemic infiltration
Left Ventricular Ejection Fraction ≥ 45% by multigated acquisition (MUGA) scan or Echocardiogram
Patients who have undergone stem cell transplantation (SCT), autologous or allogeneic, are eligible provided that they are ≥ 8 weeks from stem cell infusion, have no active graft versus host disease (GVHD), are off immune suppression for at least 2 weeks, and do not have a history of veno-occlusive disease (VOD)
Female patients of childbearing age must have negative pregnancy test and women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 30 days after study participation
Patients must be able to give informed consent

Exclusion Criteria:

Concomitant chemotherapy, radiation therapy, or immunotherapy
Patients who are receiving any other investigational agents concurrently
Hyperleukocytosis with ≥ 30,000 blasts/microliter (uL). If using tyrosine kinase/src inhibitors (FLT-3 inhibitors), other non-cytotoxics, or leukopheresis for blast count control, the patient must be off these therapies for ≥ 24 hours prior to beginning sertraline. If using hydroxyurea for blast count control, this may be continued until up to 24 hours before starting cytarabine
Acute Progranulocytic Leukemia (APL)
Active central nervous system (CNS) leukemia
Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible
Presence of other life-threatening illness
Patients with mental deficits and/or psychiatric history that preclude them from giving informed consent or from following protocol
Pregnant women are excluded from this study due to potential teratogenic and/or abortifacient effect of this combination chemotherapy. Nursing mother should stop breastfeeding to be eligible due to potential risk for adverse events in nursing infant
Subjects with the following cardiac risk factors must be excluded: transmural myocardial infarction (MI) within prior 6 months, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack (TIA) or seizure disorder within 6 months prior to study drug administration. In addition, patients with New York Heart Association (NYHA) class III or IV heart failure will be excluded
Patients requiring treatment with other anti-depressive medications including the selective and non-selective monoamine oxidase (MAO) inhibitors (including linezolid), 5-hydroxytryptamine (5-HT) receptor agonists (triptans), tryptophan or antidopaminergic agents (anti-psychotics, metoclopramide, promethazine, haloperidol)
Patients requiring prolonged treatment with fluconazole, voriconazole, or posaconazole. Use of isavuconazonium sulfate, liposomal amphotericin, are echinocandins are permitted
Prior treatment with clofarabine within 6 months or history of clofarabine-induced liver dysfunction
History of hypersensitivity to sertraline
Patients taking sertraline at the time of study entry will not be eligible for the study