NCT01567059

Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

A Phase II Study of Tosedostat in Combination With Either Cytarabine or Decitabine in Newly Diagnosed AML or High-Risk MDS

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study examines a new oral chemotherapy drug called tosedostat, in combination with cytarabine or decitabine. Tosedostat is thought to work by decreasing the availability of amino acids (building blocks the cell needs to make proteins) in cells. It has been shown in early studies to have activity against a variety of cancers, including leukemias. Patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) with specific genetic mutations have a poorer response to chemotherapy and a higher risk of relapse after treatment. Researchers are looking to see if combinations of chemotherapy drugs may improve outcomes for patients that do not respond as well with the current chemotherapy regimens, without increasing the risks of treatment.

Detailed description

PRIMARY OBJECTIVES: I. To determine the 4 month survival and complete remission (CR) rates of tosedostat in combination with either cytarabine or decitabine in untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: I. To assess safety and tolerability of tosedostat in combination with either cytarabine or decitabine. II. To determine the treatment related mortality defined as death within the first 30 days of beginning treatment. III. To estimate rates of disease-free survival (DFS) and the 1 year overall survival (OS). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive tosedostat orally (PO) once daily (QD) on days 1-35 and cytarabine intravenously (IV) on days 1-5. ARM II: Patients receive tosedostat PO QD on days 1-35 and decitabine IV on days 1-5. If the patient develops a significant increase in their circulating or bone marrow blast count, the subsequent cycle may be started as early as day 21 of the current cycle. In both arms, treatment repeats every 35 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or partial CR (pCR) may receive 2 additional courses of treatment. After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.

Conditions

• Acute Myeloid Leukemia With Multilineage Dysplasia
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• de Novo Myelodysplastic Syndromes
• Previously Treated Myelodysplastic Syndromes
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndromes
• Untreated Adult Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	tosedostat	Given PO
DRUG	cytarabine	Given IV
DRUG	decitabine	Given IV

Timeline

• Start date: 2012-05-01
• Primary completion: 2013-06-01
• Completion: 2013-06-01
• First posted: 2012-03-30
• Last updated: 2017-02-15

Locations

1 site across 1 country: United States