Aflibercept in Treating Patients With Myelodysplastic Syndromes

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed myelodysplastic syndromes (MDS), including any of the following:

  * Secondary MDS
  * MDS/myeloproliferative disorders (MPD) (e.g., chronic myelomonocytic leukemia or atypical chronic myeloid leukemia)
  * IPSS scores of 0.5 or greater (≥ INT-1) OR transfusion dependent despite use of growth factors
  * No more than 20% blasts in the marrow
  * Patients who have not responded after 3 courses of hypomethylating agents (azacitidine or decitabine) OR; who are unable to tolerate hypomethylating agents OR who refused to receive hypomethylating agents are eligible for this study
* ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
* AST/ALT ≤ 2.5 x ULN
* Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min
* Urine protein:creatinine ratio \< 1 OR urine protein \< 500 mg by 24-hour urine collection
* PT INR ≤ 1.5
* Patients with PT INR \> 1.5 on full-dose anticoagulants (e.g., warfarin) are eligible provided both of the following criteria are met:

  * Patient has an in-range INR (usually between 2 and 3) and is on a stable dose of oral anticoagulant or low molecular weight heparin
  * Patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
* Not pregnant or nursing
* Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
* Prior DNA-demethylating agent therapy or lenalidomide therapy allowed
* Prior treatment with other molecular agents, such as thalidomide, valproic acid, or imatinib mesylate allowed

Exclusion Criteria:

* Evidence of active malignancies other than squamous cell or basal cell carcinoma of the skin
* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in the study
* Serious or non-healing wound, ulcer, or bone fracture
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
* Significant traumatic injury within the past 28 days
* Clinically significant cardiovascular disease, including any of the following:

  * History of cerebrovascular accident (CVA) within the past 6 months
  * Uncontrolled hypertension, defined as blood pressure \> 150/100 mm Hg or systolic BP \> 180 mm Hg if diastolic blood pressure \< 90 mm Hg (on at least 2 repeated determinations on separate days) within the past 3 months
  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association class III or IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris within the past 6 months
* Clinically significant peripheral vascular disease within the past 6 months
* Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within the past 6 months
* Evidence of bleeding diathesis or coagulopathy
* Concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situation that would limit compliance with study requirements
* Prior cytotoxic chemotherapy for MDS
* Molecular therapy or immunosuppressive agents (including steroids) within the past 3 weeks
* Other prior antiangiogenesis agents
* Coronary artery bypass graft (CABG) within the past 6 months
* Valproic acid should be discontinued at least 24 hours before aflibercept administration, unless needed for seizure control
* Major surgical procedure or open biopsy within the past 28 days
* Core biopsy (other than bone marrow biopsy) within the past 7 days
* Anticipation of need for major surgical procedures during the course of the study
* Patients may not be receiving any other investigational agents