Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00118287
First received: July 8, 2005
Last updated: February 17, 2012
Last verified: February 2012

July 8, 2005
February 17, 2012
April 2005
October 2008   (final data collection date for primary outcome measure)
Frequency of hematologic responses, as defined by International Working Group (IWG) criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
A two-stage Simon design for phase II trials will be followed. The operating characteristics of this design yield a 90% chance of declaring a treatment ineffective if they true response rate is 0.30. If the true response rate is 0.50, there is an 80% chance of reaching the threshold of 13 responses out of 32 patients.
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Complete list of historical versions of study NCT00118287 on ClinicalTrials.gov Archive Site
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Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes
Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.

This phase I/II trial studies how well giving azacitidine together with etanercept works in treating patients with myelodysplastic syndromes (MDS). Drugs used in chemotherapy, such as azacitidine, works in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as etanercept, may protect normal cells from the side effects of chemotherapy

PRIMARY OBJECTIVES:

I. Determine the frequency of hematologic responses in patients with MDS to 5-aza (azacitidine) plus etanercept.

II. Determine the efficacy of 5-aza combined with etanercept in patients with low or intermediate (int)-1 risk who fail to respond to anti-thymocyte globulin (ATG) plus etanercept and for the purpose of this trial are considered as having progressive or "more advanced" disease.

III. Correlate results of ex vivo/in vitro studies on phenotypic, cytogenetic and functional disease characteristics with in vivo treatment responses, to identify parameters that are associated with a high probability of response.

OUTLINE:

Patients receive etanercept subcutaneously (SC) twice weekly during weeks 1 and 2 and azacitidine SC or intravenously (IV) over 10-40 minutes on days 1-7. Treatment repeats every 28 days for at least 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity.

Interventional
Phase 1
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • de Novo Myelodysplastic Syndromes
  • Previously Treated Myelodysplastic Syndromes
  • Secondary Myelodysplastic Syndromes
  • Drug: azacitidine
    Given SC or IV
    Other Names:
    • 5-AC
    • 5-azacytidine
    • azacytidine
    • Vidaza
  • Biological: etanercept
    Given SC
    Other Names:
    • Enbrel
    • ETN
    • TNFR:Fc
    • Tumor Necrosis Factor Receptor IgG Chimera
Experimental: Treatment (chemotherapy, chemoprotection)
Patients receive etanercept SC twice weekly during weeks 1 and 2 and azacitidine SC or IV over 10-40 minutes on days 1-7. Treatment repeats every 28 days for at least 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: azacitidine
  • Biological: etanercept
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
Not Provided
October 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Int-2 or high risk MDS patients
  • Patients with low-risk or int-1 risk MDS by International Prognostic Scoring System (IPSS) criteria with:

    • Single or multilineage cytopenia (absolute neutrophil count [ANC] < 1500/μL, hemoglobin [Hgb],10g/dL, or platelet count < 100,000/μL); or
    • Transfusion requirement of at least 2 units of packed red blood cells over an 8 week period
  • Serum creatinine =< 1.5x ULN (upper limit of normal)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2x ULN
  • Performance status =< 2 (Eastern Cooperative Oncology Group [ECOG] scale, 0-5)

Exclusion Criteria:

  • Patients who have previously received hematopoietic stem cell transplants, specifically for MDS
  • Patients with a diagnosis of acute myeloid leukemia (AML) by World Health Organization (WHO) criteria (i.e >= 20% blasts) at time of enrollment
  • Women of child bearing potential who are currently pregnant, lactating or who are not willing to use contraception during the entire duration of the study
  • Men who are unwilling to use contraception while receiving 5-aza
  • Patients with severe disease other than MDS which is expected to prevent compliance with the present protocol
  • Patients with severe infections (pneumonia, septicemia, etc) within the 2 weeks prior to the anticipated start of protocol treatment
  • Patients who are currently receiving or within the preceding 2 weeks have received cytotoxic therapy, hemopoietic growth factors, immunomodulatory therapy, or other experimental therapy for the treatment of MDS
  • Current evidence of uncontrolled cardiac arrhythmia or congestive heart failure
  • Platelet count =< 10,000/mcl
  • Absolute neutrophil count =< 250/mcl
  • Prior treatment with 5-aza
  • Known or suspected hypersensitivity to azacitidine or mannitol
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00118287
1926.00, NCI-2011-01818
Yes
Scott, Bart, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
National Cancer Institute (NCI)
Principal Investigator: Bart Scott Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
February 2012

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