RATIONALE: Vatalanib may be effective in preventing the development of leukemia in patients who have myelodysplastic syndromes.

PURPOSE: Phase II trial to study the effectiveness of vatalanib in treating patients who have primary or secondary myelodysplastic syndromes.

Condition	Treatment or Intervention	Phase
Chronic Myelomonocytic Leukemia myelodysplastic and myeloproliferative disease Myelodysplastic Syndromes	Drug: vatalanib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the response rate, in terms of hematologic improvement and complete and partial remission, in patients with primary or secondary (therapy-related) myelodysplastic syndromes treated with vatalanib.
• Determine the time to transformation to acute myeloid leukemia (at least 20% blasts) or death in patients treated with this drug.

Secondary

• Determine the safety of this drug in these patients.
• Determine the duration of response in patients treated with this drug.
• Determine the cytogenetic response rate in patients treated with this drug.
• Determine the overall and progression-free survival of patients treated with this drug.
• Determine the incidence of infections requiring antibiotics or hospitalization or bleeding requiring red blood cell transfusions in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to risk group (low grade vs high grade).

Patients receive oral vatalanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 6 additional courses after documentation of a CR.

Patients are followed every 6 months for up to 5 years from study entry.

PROJECTED ACCRUAL: Approximately 144 patients will be accrued for this study within 2.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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
• 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 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
• Must be registered on and CALGB-9665

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

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
• No other malignancy within the past year

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

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States; Recruiting
California
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States; Recruiting
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States; Recruiting
      Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Recruiting
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States; Recruiting
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States; Recruiting
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States; Recruiting
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States; Recruiting
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States; Recruiting
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States; Recruiting
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States; Recruiting
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States; Recruiting
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States; Recruiting
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States; Recruiting
      Memorial Cancer Institute at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States; Recruiting
      Palm Beach Cancer Institute - West Palm Beach, West Palm Beach,  Florida,  33401,  United States; Recruiting
Illinois
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States; Recruiting
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States; Recruiting
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States; Recruiting
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States; Recruiting
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States; Recruiting
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States; Recruiting
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States; Recruiting
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States; Recruiting
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States; Recruiting
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States; Recruiting
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States; Recruiting
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States; Recruiting
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States; Recruiting
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States; Recruiting
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States; Recruiting
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States; Recruiting
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States; Recruiting
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States; Recruiting
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States; Recruiting
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States; Recruiting
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting
      North Shore University Hospital, Manhasset,  New York,  11030,  United States; Recruiting
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States; Recruiting
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States; Recruiting
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States; Recruiting
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Cape Fear Valley Medical Center, Fayetteville,  North Carolina,  28302-2000,  United States; Recruiting
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States; Recruiting
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States; Recruiting
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States; Recruiting
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States; Recruiting
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805-9913,  United States; Recruiting
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States; Recruiting
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States; Recruiting
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Pennsylvania
      Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States; Recruiting
Rhode Island
      Miriam Hospital at Lifespan, Providence,  Rhode Island,  02906,  United States; Recruiting
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States; Recruiting
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States; Recruiting
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States; Recruiting
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States; Recruiting
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States; Recruiting
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States; Recruiting
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States; Recruiting
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States; Recruiting

Study chairs or principal investigators

Pankaj Gupta, MD,  Study Chair,  Veterans Affairs Medical Center - Minneapolis   

Study ID Numbers:  CDR0000339810; CALGB-10105; NCT00072475
Record last reviewed:  December 2004
Last Updated:  April 5, 2005
Record first received:  November 4, 2003
ClinicalTrials.gov Identifier:  NCT00072475
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08