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.
- 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
- 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 [refractory anemia with or without ringed sideroblasts, refractory anemia with excess
blasts-1, refractory cytopenia with multilineage dysplasia with or without ringed
sideroblasts, myelodysplastic syndromes-unclassified, or chronic myelomonocytic leukemia-1]
vs high grade [refractory anemia with excess blasts-2 or chronic myelomonocytic
leukemia-2]).
NOTE: *Stratification according to risk (low vs high) does not occur after 11/30/06.
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 periodically for up to 5 years from study entry.
PROJECTED ACCRUAL: Approximately 144 patients will be accrued for this study within 2. 5
years.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Tunnell Cancer Center at Beebe Medical Center, Lewes, Delaware 19958, United States
CCOP - Christiana Care Health Services, Newark, Delaware 19713, United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital, Fort Lauderdale, Florida 33308, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center, Jupiter, Florida 33458, United States
CCOP - Mount Sinai Medical Center, Miami Beach, Florida 33140, United States
Graham Hospital, Canton, Illinois 61520, United States
Memorial Hospital, Carthage, Illinois 62321, United States
Eureka Community Hospital, Eureka, Illinois 61530, United States
Evanston Northwestern Healthcare - Evanston Hospital, Evanston, Illinois 60201-1781, United States
Galesburg Clinic, PC, Galesburg, Illinois 61401, United States
Galesburg Cottage Hospital, Galesburg, Illinois 61401, United States
Mason District Hospital, Havana, Illinois 62644, United States
Hopedale Medical Complex, Hopedale, Illinois 61747, United States
McDonough District Hospital, Macomb, Illinois 61455, United States
BroMenn Regional Medical Center, Normal, Illinois 61761, United States
Community Cancer Center, Normal, Illinois 61761, United States
Community Hospital of Ottawa, Ottawa, Illinois 61350, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa, Ottawa, Illinois 61350, United States
Cancer Treatment Center at Pekin Hospital, Pekin, Illinois 61554, United States
CCOP - Illinois Oncology Research Association, Peoria, Illinois 61615, United States
Methodist Medical Center of Illinois, Peoria, Illinois 61636, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria, Peoria, Illinois 61615, United States
Proctor Hospital, Peoria, Illinois 61614, United States
Illinois Valley Community Hospital, Peru, Illinois 61354, United States
Perry Memorial Hospital, Princeton, Illinois 61356, United States
Center for Cancer Care at OSF Saint Anthony Medical Center, Rockford, Illinois 61108, United States
St. Margaret's Hospital, Spring Valley, Illinois 61362, United States
Elkhart General Hospital, Elkhart, Indiana 46515, United States
Fort Wayne Medical Oncology and Hematology, Fort Wayne, Indiana 46815, United States
CCOP - Northern Indiana CR Consortium, South Bend, Indiana 46601, United States
Memorial Hospital of South Bend, South Bend, Indiana 46601, United States
Central Maine Comprehensive Cancer Center at Central Maine Medical Center, Lewiston, Maine 04240, United States
Union Hospital Cancer Program at Union Hospital, Elkton MD, Maryland 21921, United States
Lakeland Regional Cancer Care Center - St. Joseph, St. Joseph, Michigan 49085, United States
Veterans Affairs Medical Center - Minneapolis, Minneapolis, Minnesota 55417, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia, Missouri 65203, United States
CCOP - Kansas City, Kansas City, Missouri 64131, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, Saint Louis, Missouri 63110, United States
Callahan Cancer Center at Great Plains Regional Medical Center, North Platte, Nebraska 69103, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center, Omaha, Nebraska 68124, United States
CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68106, United States
Creighton University Medical Center, Omaha, Nebraska 68131-2197, United States
Immanuel Medical Center, Omaha, Nebraska 68122, United States
Methodist Estabrook Cancer Center, Omaha, Nebraska 68114, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, United States
Cancer Institute of New Jersey at Cooper - Voorhees, Voorhees, New Jersey 08043, United States
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital, Manhasset, New York 11030, United States
Long Island Jewish Medical Center, New Hyde Park, New York 11042, United States
Mount Sinai Medical Center, New York, New York 10029, United States
SUNY Upstate Medical University Hospital, Syracuse, New York 13210, United States
Veterans Affairs Medical Center - Syracuse, Syracuse, New York 13210, United States
Faxton Regional Cancer Center, Utica, New York 13502, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina 27599-7295, United States
Presbyterian Cancer Center at Presbyterian Hospital, Charlotte, North Carolina 28233-3549, United States
Duke Comprehensive Cancer Center, Durham, North Carolina 27710, United States
Wayne Memorial Hospital, Incorporated, Goldsboro, North Carolina 27534, United States
Pardee Memorial Hospital, Hendersonville, North Carolina 28791, United States
Kinston Medical Specialists, Kinston, North Carolina 28501, United States
Wake Forest University Comprehensive Cancer Center, Winston-Salem, North Carolina 27157-1096, United States
Cancer Care Associates - Mercy Campus, Oklahoma City, Oklahoma 73120, United States
Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital, Pittsburgh, Pennsylvania 15224-1791, United States
Miriam Hospital, Providence, Rhode Island 02906, United States
Rhode Island Hospital Comprehensive Cancer Center, Providence, Rhode Island 02903, United States
Mountainview Medical, Berlin, Vermont 05602, United States
Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05401, United States
Danville Regional Medical Center, Danville, Virginia 24541, United States