Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

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