Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00425477
Recruitment Status : Unknown
Verified October 2015 by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Recruitment status was:  Active, not recruiting
First Posted : January 23, 2007
Last Update Posted : November 2, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief 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.

Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Biological: sargramostim Drug: bexarotene Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Other: flow cytometry Other: laboratory biomarker analysis Procedure: biopsy Phase 2

Detailed Description:



  • 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML
Study Start Date : November 2006
Estimated Primary Completion Date : July 2016

Primary Outcome Measures :
  1. Clinical response (complete and partial)

Secondary Outcome Measures :
  1. Clinical activity as measured by improved peripheral blood counts and changes in transfusion requirements
  2. Biological activity as measured by in vivo induction of terminal differentiation of myeloid progenitors and in vivo changes in detectable chromosomal abnormalities

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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)


  • 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00425477

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Study Chair: B. Douglas Smith, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT00425477     History of Changes
Other Study ID Numbers: J0675 CDR0000525989
P30CA006973 ( U.S. NIH Grant/Contract )
First Posted: January 23, 2007    Key Record Dates
Last Update Posted: November 2, 2015
Last Verified: October 2015

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory anemia with excess blasts
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
secondary acute myeloid leukemia
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)

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents