Sertraline Hydrochloride and Cytarabine in Treating Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia

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
• 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 (including fms related tyrosine kinase 3 [FLT-3] inhibitors), other non-cytotoxics, or leukapheresis for blast count control, the patient must be off these therapies for >= 24 hours (hrs) before starting sertraline; hydroxyurea will be allowed with sertraline but should be stopped >= 24 hours before starting cytarabine
• Serum creatinine < 2.0 mg/dL or creatinine clearance >= 50 mL/minute
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 5 x upper limit normal (ULN)
• Alkaline phosphatase =< 5 x 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 scan (MUGA) 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; 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/uL; if using tyrosine kinase/src inhibitors (including FLT-3 inhibitors), other non-cytotoxics, or leukapheresis 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, M3)
• 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; nursing mothers should stop breastfeeding to be eligible
• 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 (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, and 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