NCT01636609

Tosedostat and Cytarabine or Azacitidine in Treating Older Participants With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Phase I/II Study of Cytarabine or 5-Azacitidine Combined With Tosedostat to Evaluate the Safety and Tolerability in Older Patients With Acute Myeloid Leukemia (AML) or High Risk MDS

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of cytarabine and azacitidine and how well they work when giving together with tosedostat in treating older participants with acute myeloid leukemia or high risk myelodysplastic syndrome. Tosedostat and azacitidine may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tosedostat and cytarabine or azacitidine may work better in treating participants with acute myeloid leukemia or high risk myelodysplastic syndrome.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety profile of tosedostat (oral) in combination with cytarabine (subcutaneous \[SQ\]) or azacitidine (5-azacytidine) in patients age 60 years or older with relapsed/refractory acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS). II. To observe the anti-tumor effects of tosedostat in combination with cytarabine or 5-azacytidine, if any occur. OUTLINE: This is a phase I, dose-escalation of cytarabine and azacitidine followed by a phase II study. Participants are assigned to 1 of 2 arms. ARM I: Participants receive tosedostat orally (PO) once daily (QD) on days 1-28 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Participants receive tosedostat PO QD on days 1-28 and azacitidine intravenously (IV) over 10-40 minutes or SC for on days 1-7. Courses repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants will be followed up at 28 days and then every 3-5 months thereafter.

Conditions

• Acute Myeloid Leukemia
• High Risk Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Azacitidine	Given IV or SC
DRUG	Cytarabine	Given SC
DRUG	Tosedostat	Given PO

Timeline

• Start date: 2012-11-20
• Primary completion: 2019-07-04
• Completion: 2019-07-04
• First posted: 2012-07-10
• Last updated: 2020-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study