Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
Condition: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: vatalanib
Intervention description: Pts registered before 1/15/05 1250 mg/day PO After 1/15/05: Start w/ 750 mg/day PO; escalate q 4 wks in absence of Grade 2 or > tox (1st increase=1000mg/day; 2nd increase 1250 mg/day)
Intervention MeSH terms: Vatalanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; refractory anemia; previously treated myelodysplastic syndromes

Summary:

      RATIONALE: Vatalanib may be effective in preventing the development of leukemia in patients
      who have myelodysplastic syndromes.

      PURPOSE: This phase II trial is studying vatalanib to see how well it works in treating
      patients with primary or secondary myelodysplastic syndromes.
    

Eligibility 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