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

This is an interventional treatment trial for Leukemia focused on measuring untreated adult acute myeloid leukemia, recurrent adult acute myeloid leukemia Read More

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