Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Diagnosis of primary or secondary (therapy-related) myelodysplastic syndromes\* (MDS), including the following cellular types:
• •* Refractory anemia (RA)\*\*
• •* RA with excess blasts (RAEB)-1
• •* RA with ringed sideroblasts\*\*
• •* Refractory cytopenia with multilineage dysplasia
• •* Refractory cytopenia with multilineage dysplasia with ringed sideroblasts\*
• •* MDS-unclassified\*\*
• •* MDS associated with isolated del (5q)\*\*
• •* Chronic myelomonocytic leukemia (CMML)-1 NOTE: \*High-risk MDS (i.e., RAEB-2 or CMML-2) is closed to accrual as of 11/30/06
• •NOTE: \*\*Accompanied with at least 1 of the following laboratory values: hemoglobin less than 10 g/dL, platelet count less than 50,000/mm3, or absolute neutrophil count less than 1,000/mm3
• •No prior leukemia (i.e., 20% or greater blasts)
• •No prior primary or metastatic brain tumor or carcinomatous meningitis
• •PATIENT CHARACTERISTICS:
• •Age
• •18 and over
• •Performance status
• •WHO 0-2
• •Life expectancy
• •Not specified
• •Hematopoietic
• •See Disease Characteristics
• •Hepatic
• •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• •AST no greater than 2.5 times ULN
• •APTT no greater than 1.5 times ULN
• •INR no greater than 1.5
• •Renal
• •Creatinine no greater than 1.5 times ULN
• •Urine protein negative by urinalysis
• •* Protein 1+ by dipstick allowed provided total urine protein no greater than 500 mg AND creatinine clearance at least 50 mL/min by 24-hour urine collection
• •Cardiovascular
• •No significant cardiac or vascular events within the past 6 months, including any of the following:
• •* Acute myocardial infarction
• •* Unstable angina
• •* Uncontrolled hypertension
• •* Severe peripheral vascular disease (e.g., ischemic pain at rest or nonhealing ulcers or wounds)
• •* New York Heart Association class II-IV congestive heart failure
• •* Cardiac arrhythmia
• •* Disseminated intravascular coagulation or other coagulopathies
• •* Deep vein or arterial thrombosis
• •No history of congenital long QTc syndrome or elongated QTc (\> 450 msec for males or 470 for females)
• •Pulmonary
• •No pulmonary embolism within the past 6 months
• •Other
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
• •No need for full anticoagulation within the past 6 months
• •No significant hemorrhage (e.g., visceral, gastrointestinal, genitourinary, or gynecological) requiring red blood cell transfusion within the past month
• •No known cerebral aneurysms, other cerebrovascular malformations, or CNS bleeding
• •No unhealed fractures, wounds, or ulcers
• •PRIOR CONCURRENT THERAPY:
• •Biologic therapy
• •More than 12 months since prior autologous stem cell or allogeneic transplantation
• •More than 6 months since prior antiangiogenic agents
• •More than 1 month since prior interferon for MDS
• •More than 1 month since prior hematopoietic growth factors for MDS
• •More than 1 month since prior epoetin alfa (EPO) for MDS
• •More than 1 month since prior thalidomide for MDS
• •More than 1 month since prior immunotherapy for MDS
• •No concurrent prophylactic growth factors or cytokines (e.g., filgrastim \[G-CSF\], sargramostim \[GM-CSF\], EPO or EPO-derivatives, or interleukin-11)
• •Chemotherapy
• •No prior low-dose antimetabolites for MDS (e.g., hydroxyurea, azacitidine, or low-dose cytarabine)
• •More than 12 months since prior chemotherapy for another disease\* NOTE: \*Not MDS or leukemia
• •Endocrine therapy
• •More than 1 month since prior corticosteroids for MDS
• •More than 1 month since prior androgens for MDS
• •Radiotherapy
• •More than 12 months since prior radiotherapy for another disease\* NOTE: \*Not MDS or leukemia
• •Surgery
• •More than 1 month since prior surgery, including needle biopsy of visceral organs and recovered
• •* Bone marrow biopsy allowed
• •More than 2 weeks since prior placement of a subcutaneous or tunneled venous access device (e.g., PortaCath or Hickman's catheter) and adequately healed
• •Other
• •No prior cytotoxic therapy for MDS
• •More than 1 month since prior administration of any of the following medications for MDS:
• •* Danazol
• •* Retinoids
• •* Amifostine
• •* Investigational agents
• •No concurrent administration of any of the following medications:
• •* Warfarin
• •* Heparin
• •* Derivatives of heparin
• •* Other anticoagulants
• •No concurrent grapefruit or grapefruit juice