A Multi-Center Phase 2 Study of VEGF Trap as a Single Agent in Acute Myeloid Leukemia

DISEASE CHARACTERISTICS:

* Acute myeloid leukemia (AML), as defined by WHO criteria and documented by morphologic examination of bone marrow aspirate and biopsy, including the following stages:

  * AML that is refractory to at least one course of induction chemotherapy
  * AML that has relapsed following one or more histologically documented complete remissions

    * Patients relapsing following chemotherapy alone, following autologous hematopoietic stem cell transplant, or following allogeneic hematopoietic stem cell transplant
  * Patients with untreated AML if they are felt not to be eligible for standard induction chemotherapy because of age or comorbidity
* No CNS disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

* ECOG performance status 0-2
* Life expectancy ≥ 60 days
* AST/ALT ≤ 2.5 times upper limit of normal (ULN)
* Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
* Urine protein:creatinine ratio \< 1 OR 24-hour urine protein \< 500 mg
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception prior to, during, and for at least 6 months after completion of study therapy

Exclusion criteria:

* Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* Serious or nonhealing wound, ulcer, or bone fracture
* History of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
* Clinically significant cardiovascular disease within the past 6 months, including any of the following:

  * History of cerebrovascular accident
  * Myocardial infarction, coronary artery bypass graft, or unstable angina
  * New York Heart Association class III-IV congestive heart failure or serious cardiac arrhythmia requiring medication
  * Clinically significant peripheral vascular disease
  * Pulmonary embolism, deep venous thrombosis, or other thromboembolic event
* Uncontrolled hypertension, defined as BP \> 150/100 mm Hg, or systolic BP \> 180 mm Hg if diastolic blood pressure is \< 90 mm Hg, on at least 2 repeated determinations on separate days within the past 3 months
* Evidence of bleeding diathesis or coagulopathy
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
* Significant traumatic injury within 28 days prior to day 1 of therapy

PRIOR CONCURRENT THERAPY:

* Recovered from all therapy
* At least 4 weeks since prior chemotherapy and radiotherapy
* At least 4 weeks since prior FDA approved agents for treatment of myelodysplastic syndromes and/or AML, including lenalidomide and arsenic trioxide
* No prior anti-VEGF, anti-VEGFR, or antiangiogenic agents (e.g., bevacizumab)
* More than 28 days since prior major surgical procedure or open biopsy
* More than 2 days since prior bone marrow aspirate/biopsy or central venous catheter placement
* No anticipation of need for major surgical procedure during the study course
* Full-dose anticoagulation (e.g., warfarin) with PT/INR \> 1.5 allowed provided that both of the following criteria are met:

  * In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant
  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known varices)
* Prior and concurrent hydroxyurea allowed for blast control

  * Hydroxyurea must be discontinued no more than 24 hrs after the first dose of aflibercept
* No HIV-positive patients on combination antiretroviral therapy
* No other concurrent investigational agents