A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML

Inclusion 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