Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

* Patient with relapsed/refractory AML for which no standard effective therapy is anticipated to result in a durable partial or complete remission
* Eastern Cooperative Oncology Group Performance (ECOG) status 0-2
* Bilirubin =\< 2.5 x upper limit of normal (ULN) unless considered Gilbert's syndrome of leukemia
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN unless considered Gilbert's syndrome of leukemia
* Partial thromboplastin time (PTT) must be \< 1.5 x ULN and international normalized ratio (INR) \< 1.5 ULN
* Phase I subjects must have calculated creatinine clearance \>= 50 ml/min by Cockcroft-Gault formula
* All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by RevAssist) of lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
* Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent
* For patients with thromboembolic risk (history of deep venous thrombosis \[DVT\]/pulmonary embolism \[PE\], on medications that increase risk of thrombolic event, etc.) able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin \[ASA\] may use warfarin or low molecular weight heparin); the risk of blood clots may also be increased when lenalidomide is combined with other drugs known to cause blood clots such as steroids, other forms of cancer drugs, hormone replacement therapy, birth control pills and erythropoietin

Exclusion Criteria:

* Known active central nervous system (CNS) disease
* The patient has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic or any investigational agents within 14 days or 5 half lives, whichever is greater, prior to drug administration on this study or has not recovered to less than grade 2 clinically significant non-hematological adverse effects/toxicities of the previous therapy except hydroxyurea up to 24 hours prior to cytarabine initiation
* The patient has a documented left ventricular ejection fraction of \< 50 %
* Active uncontrolled infection
* Symptomatic congestive heart failure
* Unstable angina pectoris or cardiac arrhythmia
* History of adrenal insufficiency
* Psychiatric illness/social situation that would limit compliance with study requirements
* Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive because of hepatitis B virus vaccine are eligible
* Any medical condition which in the opinion of the study investigator places the patient at an unacceptable high risk of toxicities
* Lactating or pregnant female (Lactating females must agree not to breast feed while taking lenalidomide)
* The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
* Any prior use of lenalidomide
* Concurrent use of other anti-cancer agents or treatments or any other investigational agent except hydroxyurea up to 24 hours prior to cytarabine initiation