Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

Previously Treated Myelodysplastic Syndromes Clinical Trial

Official title:

Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118287
• Other study ID #: 1926.00
• Secondary ID: NCI-2011-01818
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 8, 2005
• Last updated: February 17, 2012
• Start date: April 2005

Study information

• Verified date: February 2012
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• de Novo Myelodysplastic Syndromes
• Myelodysplastic Syndromes
• Preleukemia
• Previously Treated Myelodysplastic Syndromes
• Secondary Myelodysplastic Syndromes
• Syndrome

Intervention

Drug:
• azacitidine
Given SC or IV

Biological:
• etanercept
Given SC

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of hematologic responses, as defined by International Working Group (IWG) criteria	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.	Up to 2 years	No