NCT00004871已完成1 期
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)
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 1
研究概览
简要总结
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.
详细描述
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%.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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:
- •18 and over
- •Performance status:
- •Zubrod 0-2
- •Life expectancy:
- •Not specified
- •Hematopoietic:
- •See Disease Characteristics
- •Hemoglobin at least 8 g/dL (transfusion allowed)
- •Bilirubin less than 2.0 mg/dL (unless due to hemolysis or Gilbert's disease)
- •Creatinine less than 2.0 mg/dL
- •Cardiovascular:
- •No disseminated intravascular coagulation
- •No pulmonary leukostasis
- •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:
- 另有 7 项未显示
排除标准
- 未提供
研究者
研究点 (1)
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