Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00118287
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 32
• Location: 1
• Arm: 1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes	Drug: azacitidine; Biological: etanercept	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

2. 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.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study.
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Frequency of Hematologic Responses, as Defined by International Working Group (IWG) Criteria [Up to 2 years]

   Count of participants with a hematologic improvement (erythroid, platelet, or neutrophil response), assessed at 3 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Bart Scott, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bart Scott, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00118287
• Other Study ID Numbers: 1926.00; NCI-2011-01818
• First Posted: Jul 11, 2005
• Last Update Posted: May 24, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Etanercept; Azacitidine

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Chemoprotection)
Arm/Group Description	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. azacitidine: Given SC or IV etanercept: Given SC
Period Title: Overall Study
STARTED	32
COMPLETED	30
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Chemoprotection)
Arm/Group Description	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. azacitidine: Given SC or IV etanercept: Given SC
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	11 34.4%
Male	21 65.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	31 96.9%
Unknown or Not Reported	1 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.1%
White	30 93.8%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Frequency of Hematologic Responses, as Defined by International Working Group (IWG) Criteria
Description	Count of participants with a hematologic improvement (erythroid, platelet, or neutrophil response), assessed at 3 months.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Chemotherapy, Chemoprotection)
Arm/Group Description	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. azacitidine: Given SC or IV etanercept: Given SC
Measure Participants	32
Erythroid response	14 43.8%
Platelet response	8 25%
Neutrophil response	1 3.1%
No response	7 21.9%
Withdrawn from study	2 6.3%

Adverse Events

Arm/Group Title	Treatment (Chemotherapy, Chemoprotection)
Arm/Group Description	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. azacitidine: Given SC or IV etanercept: Given SC
All Cause Mortality
	Treatment (Chemotherapy, Chemoprotection)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Chemotherapy, Chemoprotection)
	Affected / at Risk (%)	# Events
Total	5/32 (15.6%)
Blood and lymphatic system disorders
Splenic rupture with splenectomy	1/32 (3.1%)
Cardiac disorders
Cardiopulmonary arrest resulting in death	1/32 (3.1%)
Hepatobiliary disorders
Gall Bladder removal with benign mass	1/32 (3.1%)
Infections and infestations
Endocarditis	1/32 (3.1%)
Nervous system disorders
CNS hemorrhages	3/32 (9.4%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/32 (3.1%)
Hemoptysis and fever	1/32 (3.1%)
Pulmonary nodule	1/32 (3.1%)
Dyspnea	1/32 (3.1%)
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Chemoprotection)
	Affected / at Risk (%)	# Events
Total	26/32 (81.3%)
Blood and lymphatic system disorders
Anemia	19/32 (59.4%)
Coagulopathy	3/32 (9.4%)
Febrile neutropenia	7/32 (21.9%)
Leukopenia	15/32 (46.9%)
Lymphopenia	16/32 (50%)
Transfusion reaction	3/32 (9.4%)
Petechia	2/32 (6.3%)
Cardiac disorders
Atrial fibrillation/flutter	3/32 (9.4%)
Congestive heart failure	6/32 (18.8%)
Elevated cardiac enzymes	3/32 (9.4%)
Hypertension	2/32 (6.3%)
Hypotension	4/32 (12.5%)
Gastrointestinal disorders
Diverticulitis	2/32 (6.3%)
Ileus	2/32 (6.3%)
Rectal or GI bleeding	6/32 (18.8%)
Nausea/Vomiting	2/32 (6.3%)
General disorders
Mouth/Gum Bleeding	2/32 (6.3%)
Fatigue	11/32 (34.4%)
Weakness	2/32 (6.3%)
Hepatobiliary disorders
Gallstones	2/32 (6.3%)
Hematuria	9/32 (28.1%)
Investigations
Hyperbilirubinemia	3/32 (9.4%)
Neutropenia	17/32 (53.1%)
Thrombocytopenia	17/32 (53.1%)
Metabolism and nutrition disorders
Dehydration, 1 with diarrhea	2/32 (6.3%)
Hyperglycemia	3/32 (9.4%)
Hyperglycemia	2/32 (6.3%)
Hyponatremia	8/32 (25%)
Musculoskeletal and connective tissue disorders
Arthritis, Joint pain	5/32 (15.6%)
Musculoskeletal pain	11/32 (34.4%)
Compression fractures	2/32 (6.3%)
Gout	2/32 (6.3%)
Limited upper extremity function, after injury	2/32 (6.3%)
Renal and urinary disorders
Renal failure	2/32 (6.3%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	6/32 (18.8%)
Dyspnea on exertion	3/32 (9.4%)
Hypoxia	7/32 (21.9%)
Pleural effusions	2/32 (6.3%)
Hemoptysis	2/32 (6.3%)
Skin and subcutaneous tissue disorders
Bleeding from cuts	2/32 (6.3%)
Hives, urticaria	3/32 (9.4%)
Squamos cell carcinoma removal	2/32 (6.3%)
Rash	2/32 (6.3%)
Vascular disorders
Hematoma	2/32 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.