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
  Purpose

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


Condition Intervention Phase
de Novo Myelodysplastic Syndromes
Previously Treated Myelodysplastic Syndromes
Secondary Myelodysplastic Syndromes
Drug: azacitidine
Biological: etanercept
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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.


Enrollment: 32
Study Start Date: April 2005
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118287

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: Bart Scott Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Scott, Bart, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00118287     History of Changes
Other Study ID Numbers: 1926.00, NCI-2011-01818
Study First Received: July 8, 2005
Last Updated: February 17, 2012
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
TNFR-Fc fusion protein
Immunoglobulin G
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 18, 2014