MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, de Novo Myelodysplastic Syndrome
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria: Diagnosis of 1 of the following: Histologically confirmed myelodysplastic syndromes (MDS) by bone marrow aspiration and/or biopsy International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high International Prognostic Scoring System (IPSS) score of intermediate-1, intermediate-2, or high Low IPSS score allowed provided patient has a clinically significant cytopenia (i.e., absolute neutrophil count < 1,000/mm^3, untransfused hemoglobin < 8 g/dL, platelet count < 20,000/mm^3, or anemia requiring transfusion) Chronic myelomonocytic leukemia Acute myeloid leukemia (AML) Relapsed or refractory disease Untreated AML allowed provided patient meets >= 1 of the following criteria: Age 60 and over AML arising in the setting of an antecedent hematologic disorder High-risk cytogenetic abnormalities Medical conditions that may compromise the ability to give cytotoxic chemotherapy as the primary modality Refused cytotoxic chemotherapy WBC < 30,000/mm3 for >= 2 weeks before study entry Acute promyelocytic leukemia allowed provided patient is in at least second relapse and has already received treatment regimens containing arsenic trioxide and isotretinoin No clinical evidence of CNS or pulmonary leukostasis or CNS leukemia Peformance status: Zubrod 0-2 Life expectancy: At least 6 months Hematopoietic: See Disease Characteristics Hemoglobin ≥ 8 g/dL (transfusion allowed) No disseminated intravascular coagulation Renal: Creatinine normal OR Creatinine clearance >= 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study treatment No untreated, active infection No other serious or uncontrolled medical condition More than 3 weeks since prior hematopoietic growth factors for this malignancy At least 3 weeks since prior hydroxyurea (2 weeks for AML patients) No concurrent hydroxyurea Recovered from all prior therapy At least 2 weeks since prior cytotoxic therapy (AML patients) More than 3 weeks since other prior therapy for this malignancy No other concurrent investigational or commercial agents or therapies for this malignancy No concurrent valproic acid Hepatic: Bilirubin normal unless due to hemolysis or Gilbert's syndrome AST and ALT =< 2.5 times upper limit of normal
Sites / Locations
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Mount Sinai Hospital
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Experimental
Arm I
Patients receive azacitidine subcutaneously on days 1-10 and oral MS-275 on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses* of MS-275 until the maximum tolerated dose (MTD) is determined. Patients receive adjusted doses of azacitidine based on clinical response. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 9 additional patients are treated at the MTD.