MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia
Condition: Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Anemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Anemia, Refractory; Myelodysplastic-Myeloproliferative Diseases; Anemia, Refractory, with Excess of Blasts; Syndrome; Recurrence
Intervention: entinostat; sargramostim
Intervention description: Given PO; Given SC
Intervention MeSH terms: Entinostat; Sargramostim; Histone Deacetylase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving MS-275 together with GM-CSF works in treating
      patients with myelodysplastic syndrome and/or relapsed or refractory acute myeloid leukemia.
      MS-275 may stop the growth of cancer cells by blocking some of the enzymes needed for cell
      growth and by blocking blood flow to the cancer. Colony-stimulating factors, such as GM-CSF,
      may increase the number of immune cells found in bone marrow or peripheral blood. Giving
      MS-275 together with GM-CSF may be an effective treatment for myelodysplastic syndrome and
      acute myeloid leukemia
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of 1 of the following diseases by bone marrow aspiration and/or biopsy:

               -  Myelodysplastic syndromes (MDS) meeting the following criteria:

               -  Must have 1 of the following subtypes:

               -  Refractory anemia (RA) (no RA with 5q-syndrome),

               -  RA with ringed sideroblasts or

               -  Refractory cytopenia with multilineage dysplasia

          -  Myelodysplastic syndromes (MDS) meeting the following criteria:

        Must have 1 of the following subtypes:

          -  Refractory cytopenia with multilineage dysplasia and ringed sideroblasts,

          -  RA with excess blasts (RAEB)-1, RAEB-2,

          -  Myelodysplastic syndromes, unclassified or

          -  Chronic myelomonocytic leukemia

               -  International Prognostic Scoring System score of intermediate-2 or high-risk

               -  Acute myeloid leukemia (AML) meeting 1 of the following criteria:

               -  Relapsed or refractory AML, including any of the following subtypes:

               -  * AML with recurrent cytogenetic abnormalities (i.e., AML with 11q23 [MLL]
                  abnormalities)

          -  AML with multilineage dysplasia

          -  AML that is therapy-related

          -  AML, not otherwise categorized (M0 [minimally differentiated], M1 [without
             maturation], M2 [with maturation], M4 [myelomonocytic leukemia], M5
             [monoblastic/monocytic leukemia], M6 [erythroid leukemia], and M7 [megakaryoblastic
             leukemia])

               -  Untreated AML

          -  Newly diagnosed patients are eligible provided they do not qualify for potentially
             curative intensive chemotherapeutic regimens

               -  Acute lymphocytic leukemia (ALL) meeting 1 of the following criteria:

          -  Relapsed or refractory ALL

          -  Patients with any measurable residual disease are eligible, including cytogenetic
             abnormalities

               -  Untreated ALL

          -  Newly diagnosed patients are eligible provided they do not qualify for potentially
             curative intensive chemotherapeutic regimens, including any of the following:

          -  Patients who have refused chemotherapy for untreated ALL

          -  Patients who are deemed to be poor candidates medically for ALL induction chemotherapy

               -  Relatively stable bone marrow function for > 7 days prior to study entry

          -  WBC count that has not doubled within the past 7 days

          -  WBC =<10,000/mm³

               -  No uncontrolled peripheral leukemia (i.e., blast count > 30,000/mm³)

               -  No active CNS disease

          -  Lumbar puncture with negative cytology required for patients with clinical symptoms of
             active CNS disease

               -  Not a candidate for a potentially curative allogeneic stem cell transplantation
                  OR considered a poor candidate for such a procedure due to age, medical
                  comorbidities, or lack of a suitable donor

               -  Hemoglobin >= 8 g/dL (transfusions allowed)

               -  Creatinine =< 2.0 mg/dL

               -  Bilirubin =< 1.6 mg/dL (unless secondary to hemolysis)

               -  AST or ALT =< 3 times upper limit of normal (unless disease-related)

               -  Not pregnant or nursing

               -  Negative pregnancy test

               -  Fertile patients must use effective contraception

               -  No untreated or progressive infections

               -  No history of intolerance to sargramostim (GM-CSF)

               -  Recovered from all treatment-related toxicities

               -  More than 2 weeks since prior therapy for AML, ALL, or MDS, including
                  chemotherapy, hematopoietic growth factors, or biologic therapy such as
                  monoclonal antibodies

               -  Concurrent hydroxyurea allowed during course 1 for control of leukocytosis if WBC
                  > 30,000/mm³

               -  ECOG performance status 0-2