Azacitidine Plus Phenylbutyrate in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|ClinicalTrials.gov Identifier: NCT00004871|
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : March 10, 2010
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Drug: azacitidine Drug: sodium phenylbutyrate||Phase 1|
- 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 Type :||Interventional (Clinical Trial)|
|Official Title:||Phase I, Dose De-Escalation to Minimal Effective Pharmacologic Dose Trial of Sodium Phenylbutyrate (PB, NSC 657802) in Combination With 5-Azacytidine (5-AZA, NSC 102816) in Patients With Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)|
|Study Start Date :||May 2000|
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004871
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231-2410|
|Study Chair:||Steven D. Gore, MD||Sidney Kimmel Comprehensive Cancer Center|