JNJ-40346527 in Treating Participants With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria: * 1\. Ability to understand and the willingness to sign a written informed consent document. * 2\. Age \>= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included. * 3\. Morphologically documented relapsed/refractory AML as defined by World Health Organization (WHO) criteria after at least 1 prior therapy for AML with the exception of hydroxyurea, and not felt to have curative treatment options per treating physician, or the patients themselves are unwilling to consider curative treatment options. * 4\. Sufficient and viable bone marrow aspirate or peripheral blood collection to use for the ex vivo sensitivity assay. * 5\. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. * 6\. Women must not be pregnant or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to start of study drug administration. * 7\. Participants must agree to use an adequate method contraception. * 8\. Must be able to take oral medications. * 9\. Adequate organ function as defined by the following: 1. Serum creatinine =\< 2 x the upper limit of normal (ULN), or glomerular filtration rate \> 20 ml/min as calculated by Cockcroft-Gault formula. 2. Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits or can be corrected with supplementation. 3. Total serum bilirubin =\< 2.5 x ULN. 4. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =\< 2.5 x ULN. Exclusion Criteria: * 1\. Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype). * 2\. Active central nervous system involvement with AML. * 3\. Concurrent active malignancy with expected survival of less than 1 year. For example, candidates with treated skin cancers, prostate cancer, breast cancer, etc. without metastatic disease are candidates for therapy since their expected survival exceeds that of relapsed or refractory AML. All subjects with concurrent malignancies will be reviewed by the principal investigator (PI) prior to enrollment. * 4\. Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28-day screening period. * 5\. Clinically significant coagulation abnormality, such as disseminated intravascular coagulation. * 6\. Participants who are currently receiving any other investigational agents. * 7\. Previous treatment with CSF-1R kinase inhibitor or CSF-1R blocking antibody. * 8\. Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis. * 9\. Untreated HIV or active hepatitis C detectable by polymerase chain reaction (PCR), or chronic hepatitis B (patients positive for hepatitis B core antibody who are receiving intravenous immunoglobulin (IVIG) are eligible if hepatitis B \[HepB\] polymerase chain reaction \[PCR\] is negative). * 10\. Known history of cerebrovascular accident, myocardial infarction, or intracranial hemorrhage within 2 months of enrollment. * 11\. Clinically significant surgery within 2 weeks of enrollment. * 12\. Per PI discretion, active infection that is not well controlled by antibacterial or antiviral therapy. * 13\. Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count. Hydroxyurea will be weaned as soon as clinically feasible. * 14\. Unwillingness to receive infusion of blood products. * 15\. Drugs that affect the CYP3A4 systems are allowed and essential for cancer patients, including anti-fungals but should be used with caution. * 16\. Patients with uncontrolled white blood cell count (defined as \> 50 K/cu mm not controlled with hydrea).