NCT00101179

MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

A Dose-Finding Trial of the Histone Deacetylase Inhibitor MS-275 (NSC 706995) in Combination With 5-Azacitidine (5AC, NSC 102816) in Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMMoL) and Acute Myeloid Leukemia (AML)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 63 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MS-275 together with azacitidine may kill more cancer cells. This phase I trial is studying the side effects and best dose of MS-275 when given together with azacitidine in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Detailed description

OBJECTIVES: I. Determine the safety and toxicity of MS-275 and azacitidine in patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. II. Determine the maximum tolerated dose and optimal phase II dose of MS-275 when combined with azacitidine in these patients. III. Determine, preliminarily, the potential therapeutic activity of this regimen in these patients. IV. Correlate MS-275 pharmacokinetics with clinical response and laboratory correlative endpoints in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of MS-275. Patients receive azacitidine subcutaneously on days 1-10 and oral MS-275 on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of MS-275 until the maximum tolerated dose (MTD) is determined. Patients receive adjusted doses of azacitidine based on clinical response. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 9 additional patients are treated at the MTD. \[Note: Patients who do not achieve hematologic improvement or partial or complete response but who have stable disease after 4 courses of therapy may receive an additional 4 courses of therapy at a higher dose than what was originally assigned\]

Conditions

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndrome
• Leukemia
• Myelodysplastic Syndrome
• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndrome

Interventions

Type	Name	Description
DRUG	Azacitidine	Given SC
DRUG	Entinostat	Given orally

Timeline

• Start date: 2004-11-03
• Primary completion: 2011-04-20
• Completion: 2014-02-03
• First posted: 2005-01-10
• Last updated: 2019-10-18

Locations

3 sites across 1 country: United States