Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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.
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
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
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Tosedostat in Combination With Either Cytarabine or Decitabine in Newly Diagnosed AML or High-Risk MDS|
- Proportion of patients alive (survival rate) [ Time Frame: 4 months after beginning treatment ] [ Designated as safety issue: No ]Success measured by improvement of survival rate to 80% from the historical 60% while not decreasing the CR rate to < 30% from the historical 50%.
- Proportion of patients achieving CR [ Time Frame: 4 months after beginning treatment ] [ Designated as safety issue: No ]Defined by Cheson et al.
|Study Start Date:||May 2012|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (tosedostat and cytarabine)
Patients receive tosedostat PO QD on days 1-35 and cytarabine IV on days 1-5.
Other Names:Drug: cytarabine
Experimental: Arm II (tosedostat and decitabine)
Patients receive tosedostat PO QD on days 1-35 and decitabine IV on days 1-5.
Other Names:Drug: decitabine
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).
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.
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||John Pagel||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|