Brief Title
Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Official Title
A Phase II Study of Tosedostat in Combination With Either Cytarabine or Decitabine in Newly Diagnosed AML or High-Risk MDS
Brief 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Proportion of patients achieving CR
Condition
Acute Myeloid Leukemia With Multilineage Dysplasia
Intervention
tosedostat
Study Arms / Comparison Groups
Arm I (tosedostat and cytarabine)
Description: Patients receive tosedostat PO QD on days 1-35 and cytarabine IV on days 1-5.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
34
Start Date
May 2012
Completion Date
June 2013
Primary Completion Date
June 2013
Eligibility Criteria
Inclusion Criteria:
- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent
- All adults >= 60 years of age with untreated AML or high-risk MDS (10-19% marrow
blasts) including those with prior myelodysplasia (MDS)/AML, therapy-related AML, AML
with trilineage dysplasia (AML-TLD), and AML with adverse cytogenetics; patients may
be enrolled if they received prior treatment with hydroxyurea to control blood counts
or demethylating agents specifically for the purpose of treating MDS
- Adults age 18 to 59 with untreated AML or high-risk MDS and a transplant-related
mortality (TRM) score of >= 9.2; previous data suggests these people would have a 25%
mortality with standard therapy, making this treatment a reasonable alternative
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2
- Serum creatinine =< 2.0 mg/dL; if serum creatinine > 2.0 mg/dL, then the estimated
glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m^2 as calculated by the
Modification of Diet in Renal Disease equation
- Serum bilirubin =< 1.5 × upper limit of normal (ULN) (in the absence of Gilbert's
syndrome)
- Aspartate transaminase (AST)/alanine transaminase (ALT) =< 3.0 × ULN
- Alkaline phosphatase =< 2.5 × ULN
- Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree
to 1 of the following: practice effective barrier contraception during the entire
study treatment period and through a minimum of 30 days after the last dose of study
drug, or completely abstain from heterosexual intercourse
- Female subject is either postmenopausal for at least 1 year before the screening
visit, is surgically sterilized or if they are of childbearing potential, agree to
practice 2 effective methods of contraception from the time of signing the informed
consent form through 30 days after the last dose of study drug, or agree to completely
abstain from heterosexual intercourse
Exclusion Criteria:
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol
- Active uncontrolled infection
- Known infection with human immunodeficiency virus (HIV)
- Medical condition, serious concurrent illness, or other extenuating circumstance that,
in the judgment of the Principal Investigator, could jeopardize patient safety or
interfere with the objectives of the study
- Uncontrolled angina or myocardial infarction within 6 months; patients with recent
myocardial infarction apparently due to medical causes unrelated to underlying cardiac
abnormalities must have a cardiac consult, and be cleared to participate in the
research by the cardiologist prior to initiation of treatment and may be enrolled at
the discretion of the primary investigator (PI) and treating physician
- Current or history of congestive heart failure New York Heart Association (NYHA) class
3 or 4, unless a screening echocardiogram (ECHO) or multiple gate acquisition scan
(MUGA) performed within 1 month prior to study screening results in a left ventricular
ejection fraction (LVEF) that is >= 45% (or institutional lower limit of normal value)
- Diagnosed or treated for another malignancy within 1 year of enrollment, with the
exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Pagel, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01567059
Organization ID
2566.00
Secondary IDs
NCI-2012-00274
Responsible Party
Sponsor
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
John Pagel, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
February 2017