Bevacizumab in Treating Patients With Myelodysplastic Syndrome

OBJECTIVES:

• Determine the hematologic responses, including changes in hemoglobin levels, neutrophil counts, platelet counts, and percentage of bone marrow blasts, in patients with myelodysplastic syndrome treated with bevacizumab.
• Determine the toxic effects of this regimen in these patients.
• Determine the tolerance in patients treated with this regimen.
• Determine bone marrow cytogenetic responses in patients treated with this regimen.
• Determine bone marrow microvessel density in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to International Prognostic Scoring System risk status (low (low or intermediate-1) vs high (intermediate-2 or high)).

Patients receive bevacizumab IV over 30-90 minutes. Treatment repeats every 2 weeks for 4-6 months in the absence of disease progression or unacceptable toxicity.

Patients are followed at weeks 1, 3, 5, 7, and 9.

PROJECTED ACCRUAL: A total of 16-25 patients will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed myelodysplastic syndrome (MDS)

• Refractory anemia (RA)
• RA with excess blasts (RAEB)
• RAEB in transformation
• RA with ringed sideroblasts
• Non-proliferative chronic myelomonocytic leukemia (WBC less than 12,000/mm^3)
• At least 1 of the following cytopenias:

• Untransfused hemoglobin no greater than 10.0 g/dL and/or red cell transfusion dependent
• Absolute neutrophil count no greater than 1,800/mm^3 (neutropenia)
• Platelet count no greater than 100,000/mm^3 (thrombocytopenia)
• No secondary MDS
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2
• Karnofsky 60-100%

Life expectancy:

• More than 4 months

Hematopoietic:

• See Disease Characteristics
• Platelet count at least 20,000/mm^3
• No hemorrhagic illness within the past 3 weeks
• No hemolysis
• No iron deficiency
• No active blood loss

Hepatic:

• AST and ALT no greater than 2.5 times upper limit of normal (ULN)
• Bilirubin no greater than 2.0 mg/dL
• INR less than 2.0
• PTT less than 1.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL
• No renal dysfunction requiring dialysis within the past 6 months
• No nephrotic syndrome within the past 6 months

Cardiovascular:

• No myocardial infraction within the past 6 months
• No severe or unstable angina within the past 6 months
• No severe peripheral vascular disease (ischemic rest pain, non-healing wound or ulcer, or tissue loss) within the past 6 months
• No uncontrolled hypertension within the past 6 months
• No transient ischemic attack within the past 6 months
• No cerebrovascular accident within the past 6 months
• No deep venous or arterial thrombosis
• No coronary artery disease
• No symptomatic congestive heart failure (New York Heart Association class II-IV heart disease)
• No cardiac arrhythmia
• No vascular illness within the past 3 weeks

Pulmonary:

• No pulmonary embolism

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other active malignancy except localized squamous cell or basal cell skin cancer

• Prior cured malignancy allowed
• No trauma within the past 3 weeks
• No significant inflammatory disease within the past 3 weeks
• No serious non-healing wound, ulcer, or bone fracture
• No hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• No other active severe disease
• No infection
• No psychiatric illness or social situation that would preclude study compliance
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior allogeneic bone marrow transplantation
• At least 30 days since prior biologic response modifiers
• At least 30 days since prior hematopoietic growth factors
• At least 30 days since prior thalidomide
• No concurrent thalidomide
• No other concurrent biologic response modifiers
• No concurrent hematopoietic growth factors (including epoetin alfa)
• Concurrent filgrastim (G-CSF) for febrile neutropenia allowed
• Concurrent transfusions allowed

Chemotherapy:

• At least 30 days since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroid therapy (more than 10 mg/day of prednisone or equivalent steroid dose) except for pre-medication for transfusions

Radiotherapy:

• At least 30 days since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• At least 3 weeks since prior surgery (including biopsy of visceral organ)

Other:

• At least 10 days since prior anticoagulants
• No concurrent cytotoxic agents
• No other concurrent investigational agents