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

January 19, 2007
January 23, 2007
November 2, 2015
November 2006
July 2016   (Final data collection date for primary outcome measure)
Clinical response (complete and partial)
Same as current
Complete list of historical versions of study NCT00425477 on Archive Site
  • Clinical activity as measured by improved peripheral blood counts and changes in transfusion requirements
  • Biological activity as measured by in vivo induction of terminal differentiation of myeloid progenitors and in vivo changes in detectable chromosomal abnormalities
Same as current
Not Provided
Not Provided
Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML

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.



  • 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.

Phase 2
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Unknown status
Not Provided
July 2016   (Final data collection date for primary outcome measure)


  • 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
Sexes Eligible for Study: All
18 Years to 120 Years   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
J0675 CDR0000525989
P30CA006973 ( U.S. NIH Grant/Contract )
Not Provided
Not Provided
Not Provided
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP