Azacitidine Plus Phenylbutyrate in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Phase 1

Completed

• Conditions: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

• Registration Number: NCT00004871
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

RATIONALE: Azacitidine plus phenylbutyrate may help leukemia cells develop into normal white blood cells.

PURPOSE: Phase I trial to study the effectiveness of combining azacitidine and phenylbutyrate in treating patients who have acute myeloid leukemia or myelodysplastic syndrome.

Detailed Description

OBJECTIVES:

* Determine the safety and toxicity of azacitidine in combination with phenylbutyrate in patients with recurrent, refractory, or untreated acute myeloid leukemia or myelodysplastic syndrome.

* Determine the minimal effective pharmacologic dose of azacitidine required to consistently inhibit DNA methyltransferase in this patient population.

* Obtain preliminary clinical and/or laboratory data suggesting potential therapeutic activity of this combination regimen in these patients.

OUTLINE: This is a dose deescalation study of azacitidine.

Patients receive azacitidine subcutaneously daily on days 1-5 and 29-33 followed by phenylbutyrate IV continuously on days 5-12 and 33-40. Treatment continues for at least 2 courses in the absence of disease progression. Patients with responsive disease may receive an additional 2 months of therapy.

Cohorts of 3-6 patients receive deescalating doses of azacitidine until the minimal effective pharmacologic dose (MEPD) is determined. The MEPD is defined as the dose above the dose at which more than 1 of 6 patients do not meet the target enzyme inhibition of greater than 90%.

Once the MEPD and toxicity have been established for a 5 day schedule, daily dose schedule of azacitidine is increased to 10, 14, and 21 days, followed by phenylbutyrate for 7 days. Courses are repeated every 28 days.

PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study within 2 years.

Study Timeline

• Study First Submitted: 2000-03-07
• Study Start: 2000-05
• Study First Submitted QC: 2003-01-26
• Study First Posted: 2003-01-27
• Status Verified: 2010-03
• Last Update Submitted: 2010-03-09
• Last Update Posted: 2010-03-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Trial Locations

Locations (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States