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

NCT01567059 | Completed Phase 2

• 3 other identifiers: 2566.00NCI-2012-00274P30CA015704
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving CR

  Defined by Cheson et al.

  4 months after beginning treatment

Study Arms (2)

Arm I (tosedostat and cytarabine)

EXPERIMENTAL

Patients receive tosedostat PO QD on days 1-35 and cytarabine IV on days 1-5.

Drug: tosedostat; Drug: cytarabine

Arm II (tosedostat and decitabine)

EXPERIMENTAL

Patients receive tosedostat PO QD on days 1-35 and decitabine IV on days 1-5.

Drug: tosedostat; Drug: decitabine

Interventions

tosedostat DRUG

Given PO

Also known as: aminopeptidase inhibitor CHR-2797, CHR-2797

Arm I (tosedostat and cytarabine); Arm II (tosedostat and decitabine)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I (tosedostat and cytarabine)

decitabine DRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC

Arm II (tosedostat and decitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

tosedostat; Cytarabine; Decitabine

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Azacitidine; Aza Compounds; Organic Chemicals; Ribonucleosides

Study Officials

• John Pagel

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2012
• First Posted: March 30, 2012
• Study Start: May 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (1)