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)

Date de début de l'étude : 1 mai 2000

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