Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Exclusion Criteria

• •Prior treatment toxicities must be resolved to ≤ grade 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
• •Patients who are currently receiving any other investigational agents
• •Patients with untreated central nervous system involvement by AML should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; this is an uncommon situation in AML and therefore a lumbar puncture for cerebrospinal fluid (CSF) sampling or magnetic resonance imaging (MRI) imaging are Not necessary to rule out central nervous system (CNS) involvement in the absence of clinical suspicion by the treating physician
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to tretinoin or lithium carbonate or other agents used in this study
• •Prohibited medications, supplements and herbal medications:
• •* Tetracycline and its derivatives (enhance the risk of retinoic acid toxicity)
• •* Live vaccines
• •* Vitamin A
• •* St. John's wort
• •* Dong quai: Herbal supplement, (Angelica sinensis)
• •* Cytochrome P450 2C8 (CYP2C8) inhibitors: gemfibrozil, trimethoprim, thiazolinediones, montelukast, quercetin
• •* CYP2C8 inducers: rifampicin
• •* Patients receiving any medications or substances that are moderate and strong inhibitors of CYP2C8 or inducers of CYP2C8 are ineligible
• •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• •Pregnant or breastfeeding women are excluded from this study because tretinoin is a retinoid derivative agent with the potential for teratogenic or abortifacient effects; because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with tretinoin, breastfeeding should be discontinued if the mother is treated with tretinoin; these potential risks may also apply to other agents used in this study
• •Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with tretinoin; in addition, these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• •Chronic active hepatitis B or C infection
• •Previous diagnosis of bipolar disorder
• •Known hypersensitivity to lithium or tretinoin
• •Personal or family history of established Brugada syndrome; if pre-enrollment electrocardiogram (ECG) demonstrates abnormal findings (ST elevation in precordial leads), cardiology consultation should be obtained to rule out presence of this inherited syndrome; patients with family history of unexplained sudden death before the age 45 years; personal history of unexplained syncope or history of unexplained ventricular tachycardia or fibrillation should have a cardiology evaluation to rule out the diagnosis of Brugada syndrome