Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

NCT ID: NCT00118287

Last Updated: 2017-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30

Brief Summary

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

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.

Conditions

de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Given SC or IV

etanercept

Intervention Type: BIOLOGICAL

Given SC

Interventions

azacitidine

Given SC or IV

Intervention Type: DRUG

etanercept

Given SC

Intervention Type: BIOLOGICAL

Other Intervention Names

5-AC; 5-azacytidine; azacytidine; Vidaza; Enbrel; ETN; TNFR:Fc; Tumor Necrosis Factor Receptor IgG Chimera

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Bart Scott

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bart Scott

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2011-01818

Identifier Type: REGISTRY

Identifier Source: secondary_id

1926.00

Identifier Type: -

Identifier Source: org_study_id