Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
Condition: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: sargramostim; bexarotene; cytogenetic analysis; fluorescence in situ hybridization; flow cytometry; laboratory biomarker analysis; biopsy
Intervention MeSH terms: Bexarotene; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: refractory anemia with excess blasts; recurrent adult acute myeloid leukemia; untreated adult acute myeloid leukemia; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; myelodysplastic/myeloproliferative disease, unclassifiable; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; chronic myelomonocytic leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult pure erythroid leukemia (M6b); adult erythroleukemia (M6a); adult acute megakaryoblastic leukemia (M7); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with inv(16)(p13;q22)

Summary:

      RATIONALE: Bexarotene may help cancer or abnormal cells become more like normal cells, and to
      grow and spread more slowly. Colony-stimulating factors, such as GM-CSF, may increase the
      number of immune cells found in bone marrow or peripheral blood. Giving bexarotene together
      with GM-CSF may be an effective treatment for myelodysplastic syndrome (MDS) or acute myeloid
      leukemia.

      PURPOSE: This phase II trial is studying how well giving bexarotene together with GM-CSF
      works in treating patients with MDS or acute myeloid leukemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis (confirmed by bone marrow aspirate and/or biopsy) of 1 of the following:

               -  Myelodysplastic syndromes of 1 of the following cell types:

                    -  Refractory anemia (RA) with ringed sideroblasts

                    -  Refractory cytopenia with multilineage dysplasia (RCMD)

                    -  RCMD and ringed sideroblasts

                    -  RA with excess blasts-1

                    -  RA with excess blasts-2

                    -  Myelodysplastic syndromes, unclassified

                    -  Chronic myelomonocytic leukemia

               -  Relapsed or refractory acute myeloid leukemia (AML), meeting 1 of the following
                  criteria:

                    -  Recurrent genetic abnormalities (11q23 [MLL] abnormalities)

                    -  Multilineage dysplasia

                    -  Therapy-related AML

                    -  Not otherwise categorized, including any of the following:

                         -  M0 minimally differentiated

                         -  M1 without maturation

                         -  M2 with maturation

                         -  M4 myelomonocytic leukemia

                         -  M5 monoblastic/monocytic leukemia

                         -  M6 erythroid leukemia

                         -  M7 megakaryoblastic leukemia

          -  Newly diagnosed untreated AML allowed provided patient does not qualify for or refused
             potentially curative intensive chemotherapeutic regimens

          -  No RA with 5q-syndrome

          -  No peripheral leukemia with blast count > 30,000/mm³ (uncontrolled with hydroxyurea)

          -  Relatively stable bone marrow function for > 7 days (i.e., no WBC doubling to >
             10,000/mm^3)

          -  No acute promyelocytic leukemia

          -  No clinical symptoms of active CNS disease (if CNS disease is suspected, patient must
             have lumbar puncture with negative cytology)

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  Creatinine ≤ 2.0 mg/dL

          -  Bilirubin ≤ 1.6 mg/dL (unless secondary to hemolysis)

          -  AST and ALT ≤ 4 times upper limit of normal (unless disease related)

          -  Hemoglobin ≥ 8 g/dL (transfusions allowed)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective barrier contraception

          -  No untreated positive blood cultures or progressive infection as assessed by
             radiographic studies

          -  No history of intolerance to sargramostim (GM-CSF)

        PRIOR CONCURRENT THERAPY:

          -  Recovered from prior therapy

          -  At least 2 weeks since prior treatment for myeloid disorder, including any of the
             following:

               -  Chemotherapy

               -  Hematopoietic growth factors

               -  Biologic therapy (e.g., monoclonal antibodies)

          -  Hydroxyurea for patients with WBC > 10,000/mm^3 allowed

          -  No concurrent vitamin A supplementation

          -  No concurrent gemfibrozil