Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
Status and phase
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Treatments
Study type
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Details and patient eligibility
About
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.
Full description
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 [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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion 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
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Creatinine no greater than 1.5 times ULN
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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
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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
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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
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More than 1 month since prior surgery, including needle biopsy of visceral organs and recovered
- Bone marrow biopsy allowed
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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
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No prior cytotoxic therapy for MDS
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More than 1 month since prior administration of any of the following medications for MDS:
- Danazol
- Retinoids
- Amifostine
- Investigational agents
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No concurrent administration of any of the following medications:
- Warfarin
- Heparin
- Derivatives of heparin
- Other anticoagulants
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No concurrent grapefruit or grapefruit juice
Trial design
Primary purpose
Allocation
Interventional model
Masking
155 participants in 1 patient group
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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