A Phase II Study of VEGF Trap (NSC 724770) in Patients With MDS

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