Aflibercept in Treating Patients With Myelodysplastic Syndromes

• 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