MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

• Status: Completed
• Trial end date: 2014-02-03
• Target enrollment: 0
• Participant gender: All

Summary

MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MS-275 together with azacitidine may kill more cancer cells. This phase I trial is studying the side effects and best dose of MS-275 when given together with azacitidine in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Azacitidine; Entinostat; Histone Deacetylase Inhibitors

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