Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.
18 Years
N/A
Both
de Novo Myelodysplastic Syndromes, Previously Treated Myelodysplastic Syndromes, Secondary Myelodysplastic Syndromes
Trial Information
Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Frequency of hematologic responses, as defined by International Working Group (IWG) criteria
Outcome Description:
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.
Outcome Time Frame:
Up to 2 years
Safety Issue:
No
Principal Investigator
Bart Scott
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Federal Government
Study ID:
1926.00
NCT ID:
NCT00118287
Start Date:
April 2005
Completion Date:
Related Keywords:
- de Novo Myelodysplastic Syndromes
- Previously Treated Myelodysplastic Syndromes
- Secondary Myelodysplastic Syndromes
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
