Inclusion Criteria:

* Diagnosis of MDS or CMML according to World Health Organization (WHO) and low or intermediate-1 risk by International Prognostic Scoring System (IPSS) or revised International Prognostic Scoring System (IPSS-R) with a score of =\< 3.5
* Patients need to have not responded to prior therapy with erythrocyte stimulating agents (ESAs) or hypomethylating agents (HMAs). These could include azacitidine, decitabine, SGI-110, ASTX727, or CC-486. Patients will need to have received at least 4 cycles of HMA. Patients with relapse or progression after any number of cycles of HMA by International Working Group (IWG) 2006 criteria will also be candidates. Patients with evidence of del 5q alteration also are required to have been treated with lenalidomide
* Hemoglobin \< 10 g/dL with symptomatic anemia or transfusion dependency defined as the need for prior transfusion in the past 8 weeks for a hemoglobin level less than 8 g/dl
* Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study
* Total bilirubin =\< 3 X upper limit of normal (ULN)
* Aspartate transaminase (AST) or alanine transferase (ALT) =\< 3 X ULN
* Serum creatinine clearance \> 30mL/min and no end/stage renal disease (using Cockcroft-Gault)
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
* Hydroxyurea for control of leukocytosis is allowed at any time prior to or during study if considered to be in the best interest of the patient

Exclusion Criteria:

* No prior therapy for MDS
* Uncontrolled infection not adequately responding to appropriate antibiotics
* Absolute neutrophil count (ANC) \< 0.5 X 10\^9 k/ul
* Female patients who are pregnant or lactating
* Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], double-barrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months.
* Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
* History of an active malignancy within the past 2 years prior to study entry, with the exception of:

* Adequately treated in situ carcinoma of the cervix uteri
* Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
* Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)