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

Phase 2
18 Years
Open (Enrolling)
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

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



- Assess the clinical response in patients with myelodysplastic syndromes or acute
myeloid leukemia treated with bexarotene and sargramostim (GM-CSF).


- Determine the clinical activity of this regimen, in terms of transfusion requirements,
in these patients.

- Determine the biological activity of this regimen, in terms of biological markers and
cytogenetic abnormalities, in these patients.

- Assess the toxicity profile of this regimen in these patients.

OUTLINE: Patients receive oral bexarotene and sargramostim (GM-CSF) subcutaneously on days
1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity.

Blood and bone marrow samples are collected at baseline and after 1 or 2 courses of study
therapy. Samples are examined by flow cytometry for laboratory studies, including biological
markers, and by fluorescent in situ hybridization (FISH) for cytogenetic changes.

After completion of study treatment, patients are followed periodically for 6 months.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Inclusion Criteria


- 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

- 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 >

- No acute promyelocytic leukemia

- No clinical symptoms of active CNS disease (if CNS disease is suspected, patient must
have lumbar puncture with negative cytology)


- 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)


- Recovered from prior therapy

- At least 2 weeks since prior treatment for myeloid disorder, including any of the

- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical response (complete and partial)

Safety Issue:


Principal Investigator

B. Douglas Smith, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:

J0675 CDR0000525989



Start Date:

November 2006

Completion Date:

December 2013

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • 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)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410