Expired Study
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Baltimore, Maryland 21231


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.

Study summary:

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.


DISEASE CHARACTERISTICS: - Histologically or cytologically confirmed myelodysplastic syndrome (MDS) indicating one of the following: - Refractory anemia (RA) - Primary refractory leukopenia or thrombocytopenia with MDS morphology - RA with excess blasts (RAEB) - RA with ringed sideroblasts (RARS) - Chronic myelomonocytic leukemia - RAEB in transformation - RA or RARS must have at least one of the following: - Absolute neutrophil count less than 1,000/mm^3 - Untransfused hemoglobin less than 8 g/dL - Platelet count less than 20,000/mm^3 - Anemia - Thrombocytopenia requiring transfusion - High risk chromosomal abnormalities - Any stage of MDS allowed including: - Previously untreated MDS - Refractory MDS allowed if failure to achieve remission following prior intensive chemotherapy of at least 1 month ago - Relapsed, refractory, or untreated acute myeloid leukemia (AML) with the following: - WBC less than 30,000/mm^3 - Stable for at least 2 weeks - Unlikely to require cytotoxic therapy during study - Untreated AML with poor risk factors for response to standard therapy including: - Greater than 60 years old - AML occurs in setting of antecedent hematologic disorder - High risk chromosomes (e.g., abnormalities of chromosome 5 or 7 or complex cytogenetic abnormalities) - Medical conditions that preclude cytotoxic chemotherapy as primary therapy - Refusal of cytotoxic chemotherapy allowed - No clinical evidence of CNS leukostasis or CNS leukemia PATIENT CHARACTERISTICS: Age: - 18 and over Performance status: - Zubrod 0-2 Life expectancy: - Not specified Hematopoietic: - See Disease Characteristics - Hemoglobin at least 8 g/dL (transfusion allowed) Hepatic: - Bilirubin less than 2.0 mg/dL (unless due to hemolysis or Gilbert's disease) Renal: - Creatinine less than 2.0 mg/dL Cardiovascular: - No disseminated intravascular coagulation Pulmonary: - No pulmonary leukostasis Other: - No active infection - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception 2 weeks prior, during and 3 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: - At least 3 weeks since prior biologic therapy including colony stimulating factors and recovered Chemotherapy: - See Disease Characteristics - At least 3 weeks since prior chemotherapy and recovered Endocrine therapy: - At least 3 weeks since prior hormonal therapy and recovered Radiotherapy: - At least 3 weeks since prior radiotherapy and recovered Surgery: - Not specified



Primary Contact:

Study Chair
Steven D. Gore, MD
Sidney Kimmel Comprehensive Cancer Center

Backup Contact:


Location Contact:

Baltimore, Maryland 21231
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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