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Differentiation Therapy With Decitabine in Treating Patients With Myelodysplastic Syndrome

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ClinicalTrials.gov Identifier: NCT01165996
Recruitment Status : Completed
First Posted : July 20, 2010
Results First Posted : February 26, 2013
Last Update Posted : March 4, 2019
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Myelomonocytic Leukemia
de Novo Myelodysplastic Syndromes
Myelodysplastic Syndromes
Refractory Anemia
Refractory Anemia With Excess Blasts
Refractory Anemia With Ringed Sideroblasts
Refractory Cytopenia With Multilineage Dysplasia
Thrombocytopenia
Interventions Other: flow cytometry
Other: DNA methylation analysis
Other: cytogenetic analysis
Drug: decitabine
Genetic: microarray analysis
Genetic: gene expression analysis
Other: pharmacological study
Genetic: polymorphism analysis
Enrollment 25
Recruitment Details Patients were recruited from medical clinic between July 2010 and September 2011.
Pre-assignment Details  
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 25
Induction Phase 25
Maintenance Phase 23
Completed 23
Not Completed 2
Reason Not Completed
Death             1
Physician Decision             1
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants
40-49 years 1
50-59 years 1
60-69 years 8
70-79 years 9
80-89 years 6
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
11
  44.0%
Male
14
  56.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants
25
1.Primary Outcome
Title Number of Patients With Response as Defined by IWG (International Working Group) Criteria for Myelodysplasia
Hide Description Complete Response (CR) include less than 5% marrow blasts without evidence of dysplasia and normalization of peripheral blood counts, including a hemoglobin level of 110 g/L or more, a neutrophil count of 1.5 × 109/L or more, and a platelet count of 100 × 109/L or more. For PR, patients must demonstrate all CR criteria if abnormal before treatment except that marrow blasts should decrease by 50% or more compared with pretreatment levels, or patients may demonstrate a less-advanced MDS disease category than prior to treatment. Stable disease (SD) is defined by failure to achieve at least a partial response but no evidence of progression. Disease progression (DP) includes at least 50% decrease from maximum remission in granulocytes or platelets, reduction in hemoglobin by greater than or equal to 2g/dL, or transfusion dependence. Hematologic improvement (HI) includes hemoglobin increase by at least 1.5g/dL, reduction in transfusions, increase of platelets, increase of neutrophil count
Time Frame Formal assessment at week 12 for study primary end-point (hematologic improvement).
Hide Outcome Measure Data
Hide Analysis Population Description
All patients enrolled and that received any treatment.
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:
INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
Hematologic Improvement 7
Complete Remission 4
Partial Remission 0
Stable Disease 9
Disease Progression 5
2.Secondary Outcome
Title Number of Patients That Experience > Grade 2 Non-hematologic Toxicity by National Cancer Institute (NCI)/Cancer Therapy Evaluation Program (CTEP) v4 Criteria
Hide Description Incidence of treatment-emergent adverse events (AEs) will be presented in tables that include causality, seriousness, severity/grade, and whether the AE resulted in death or discontinuation of treatment, Laboratory data will be summarized in tables that show changes from pre-treatment values and frequencies of abnormal values. Descriptive statistics will also be provided.
Time Frame up to 12 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All patients that received treatment.
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:
INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
16
3.Secondary Outcome
Title Cytogenetic Response as Per IWG Criteria
Hide Description Described as the number of patients with a major cytogenetic response (refers to disappearance of a cytogenetic abnormality) or a minor cytogenetic response (50% or more reduction of abnormal metaphases).
Time Frame at 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients that had cytogenetic abnormalities at baseline and were evaluable with follow-up metaphase karyotyping.
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:
INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
complete cytogenetic remission 5
partial cytogenetic remission 2
no cytogenetic remission 4
4.Secondary Outcome
Title Proportion of Patients With Pharmacodynamic Evidence of Drug Effect.
Hide Description Evidence of pharmacodynamic effect will be correlated with clinical response criteria. The pharmacodynamic effect of treatment is defined as the number of participants that had depletion DNMT1 with minimal DNA damage and cytotoxicity.
Time Frame 6 weeks after treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects that had treatment with DNMT1 depletion.
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts &lt; 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

flow cytometry: Correlative studies

DNA methylation analysis: Correlative studies

cytogenetic analysis: Correlative studies

decitabine: Given subcutaneously

microarray analysis: Correlative studies

gene expression analysis: Correlative studies

pharmacological study: Correlative studies

polymorphism analysis: Correlative studies

Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
25
5.Secondary Outcome
Title Proportion of Patients With Bone Marrow Evidence of Cytotoxicity.
Hide Description Cytotoxicity is the ability to destroy cells. This will be measured by taking bone marrow samples and measuring the damage to cells. The level of cell destruction will be correlated with clinical response criteria.
Time Frame 6 weeks after treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with chromosomal abnormalities which were evaluable for follow-up karyotyping
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts &lt; 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

flow cytometry: Correlative studies

DNA methylation analysis: Correlative studies

cytogenetic analysis: Correlative studies

decitabine: Given subcutaneously

microarray analysis: Correlative studies

gene expression analysis: Correlative studies

pharmacological study: Correlative studies

polymorphism analysis: Correlative studies

Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants
Complete cytogenetic remission 5
Partial cytogenetic remission 2
6.Secondary Outcome
Title Proportion of Patients With Bone Marrow Evidence of Terminal Differentiation Response to Therapy.
Hide Description Number of participants who, after therapy, had more of the differentiated types of blood (red cells, platelets, and white cells) compared to abnormal bone marrow cells than before therapy
Time Frame 6 weeks after treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts &lt; 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

flow cytometry: Correlative studies

DNA methylation analysis: Correlative studies

cytogenetic analysis: Correlative studies

decitabine: Given subcutaneously

microarray analysis: Correlative studies

gene expression analysis: Correlative studies

pharmacological study: Correlative studies

polymorphism analysis: Correlative studies

Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
11
7.Secondary Outcome
Title Proportion of Patients With Particular Genetic Abnormalities Detected by Whole Exome Sequencing Correlation With Clinical Response
Hide Description Proportion of patients with particular genetic abnormalities, including DNA Methyltransferase 1 (DNMT1) depletion, detected by whole exome sequencing correlation with clinical response
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm I: Decitabine 0.2mg/kg
Hide Arm/Group Description:

INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts &lt; 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

flow cytometry: Correlative studies

DNA methylation analysis: Correlative studies

cytogenetic analysis: Correlative studies

decitabine: Given subcutaneously

microarray analysis: Correlative studies

gene expression analysis: Correlative studies

pharmacological study: Correlative studies

polymorphism analysis: Correlative studies

Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: participants
4
Time Frame Data collected from on treatment to completion of treatment over a 1 year period.
Adverse Event Reporting Description Only grade 3 and above AEs were collected and all submitted as SAEs.
 
Arm/Group Title Arm I
Hide Arm/Group Description INDUCTION PHASE: Patients receive decitabine subcutaneously (SQ) twice weekly for 4 weeks or thrice weekly until achieving bone marrow blasts < 5%. MAINTENANCE PHASE: Patients then receive decitabine SQ twice weekly for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Arm I
Affected / at Risk (%)
Total   3/25 (12.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I
Affected / at Risk (%) # Events
Total   15/25 (60.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia * 1  10/25 (40.00%)  17
Neutropenic Fever * 1  2/25 (8.00%)  4
General disorders   
Death * 1  3/25 (12.00%)  3
fever * 1  1/25 (4.00%)  1
Left Sided Chest Pain * 1  1/25 (4.00%)  1
Infections and infestations   
bacterial infection * 1  2/25 (8.00%)  2
Sepsis * 1  1/25 (4.00%)  1
Tooth Extraction * 1  1/25 (4.00%)  1
Urinary tract infection * 1  1/25 (4.00%)  1
Metabolism and nutrition disorders   
Dehydration * 1  1/25 (4.00%)  1
Nervous system disorders   
Headache * 1  1/25 (4.00%)  1
Renal and urinary disorders   
Hematuria * 1  1/25 (4.00%)  1
Respiratory, thoracic and mediastinal disorders   
aspiration pneumonia * 1  1/25 (4.00%)  1
Skin and subcutaneous tissue disorders   
Furuncle on left groin area * 1  1/25 (4.00%)  1
Vascular disorders   
Acute Left Popliteal DVT * 1  1/25 (4.00%)  1
Hypertension * 1  1/25 (4.00%)  2
Hypotension * 1  1/25 (4.00%)  1
Orthostasis * 1  1/25 (4.00%)  2
Orthostatic Hypotension * 1  1/25 (4.00%)  1
1
Term from vocabulary, CTCAE (4.0)
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm I
Affected / at Risk (%) # Events
Total   0/0    
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Yogen Saunthararajah, MD
Organization: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Phone: 216-444-8170
Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01165996     History of Changes
Other Study ID Numbers: CASE2908
NCI-2010-00135 ( Other Identifier: NCI/CTRP )
CASE2908 ( Other Identifier: Case Comprehensive Cancer Center )
First Submitted: July 14, 2010
First Posted: July 20, 2010
Results First Submitted: January 2, 2013
Results First Posted: February 26, 2013
Last Update Posted: March 4, 2019