Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Bexarotene and GM-CSF in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), May 2008
Sponsors and Collaborators: Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00425477
  Purpose

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 Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Drug: bexarotene
Drug: sargramostim
Procedure: biopsy
Procedure: cytogenetic analysis
Procedure: flow cytometry
Procedure: fluorescence in situ hybridization
Procedure: laboratory biomarker analysis
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic
Drug Information available for: Sargramostim Granulocyte-macrophage colony-stimulating factor Bexarotene
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study of Bexarotene + Sargromastastin as Agents of Differentiation in MDS and AML

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Clinical response (complete and partial) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical activity as measured by improved peripheral blood counts and changes in transfusion requirements [ Designated as safety issue: No ]
  • Biological activity as measured by in vivo induction of terminal differentiation of myeloid progenitors and in vivo changes in detectable chromosomal abnormalities [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: November 2006
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

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

Secondary

  • 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00425477

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: B. Douglas Smith, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000525989, JHOC-J0675, JHOC-NA_00003076
Study First Received: January 19, 2007
Last Updated: October 22, 2008
ClinicalTrials.gov Identifier: NCT00425477  
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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)

Study placed in the following topic categories:
Leukemia, Monocytic, Acute
Precancerous Conditions
Chronic myelomonocytic leukemia
Refractory anemia
Acute myelomonocytic leukemia
Di Guglielmo's syndrome
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Anemia, Refractory
Bexarotene
Neoplasm Metastasis
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Congenital Abnormalities
Acute myelocytic leukemia
Myelodysplastic syndromes
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Anemia
Myeloproliferative Disorders
Acute myelogenous leukemia
Leukemia, Myeloid
Recurrence
Leukemia, Myelomonocytic, Acute
Myelodysplastic myeloproliferative disease
Leukemia, Erythroblastic, Acute
Anemia, Refractory, with Excess of Blasts

Additional relevant MeSH terms:
Anticarcinogenic Agents
Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Antineoplastic Agents
Therapeutic Uses
Syndrome
Physiological Effects of Drugs
Protective Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009