Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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.

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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Pankaj Gupta

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00072475
Information obtained from ClinicalTrials.gov on December 14, 2011

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