A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)

Date de début de l'étude : 1 décembre 2003

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