Decitabine in Treating Patients With Myelofibrosis
Study Details
Study Description
Brief Summary
This phase II trial studies the side effects and how well decitabine works in treating patients with myelofibrosis, a cancer of the blood system associated with fibrosis (scar tissue) in the bone marrow that is advanced and for which there is no standard therapy. Decitabine may block the actions of some proteins that are responsible for turning certain genes off in various cancers including myelofibrosis.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
-
To determine response rate (complete and partial responses and hematological improvement) to decitabine in patients with myelofibrosis.
-
To determine the safety of decitabine in patients with myelofibrosis.
SECONDARY OBJECTIVES:
-
To determine the effects of decitabine on specific epigenetic changes including methylation status of specific target genes and gene re-expression.
-
To determine the effect of decitabine on hemoglobin F levels and on the absolute numbers of circulating cluster of differentiation (CD) 34+ progenitor cells and to investigate the potential utility of these markers as a surrogate for biologic activity of decitabine in myeloid metaplasia with myelofibrosis (MMM).
OUTLINE:
Patients receive decitabine subcutaneously (SC) on days 1-5 and 8-12. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Treatment (decitabine) Patients receive decitabine SC on days 1-5 and 8-12. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. |
Drug: Decitabine
Given SC
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
|
Outcome Measures
Primary Outcome Measures
- Response Rate (Complete Response, Partial Response, or Hematologic Improvement. [Up to 36 weeks (6 cycles)]
Complete response is normalization of counts and transfusion-independence. Partial response is hemoglobin increase to normal levels, multilineage improvement including absolute neutrophil count (ANC) and/or platelets. Hematologic improvement is red cell transfusion-independence or >50% increase in platelet levels.
- Incidence of Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 [Up to 30 days of last dose of decitabine]
Percentage of patients experiencing any toxicity, any grade level. Additional details on adverse events are reported in Adverse Events section.
Secondary Outcome Measures
- CD34+ Cells [Cycle 1, Day 1]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CD34+ Cells [Cycle 1, Day 5]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CD34+ Cells [Cycle 1, Day 12]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CD34+ Cells [Cycle 2, Day 1]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CD34+ Cells [Cycle 2, Day 5]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CD34+ Cells [Cycle 2, Day 12]
CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously.
- CXCR4 [Cycle 1, Day 1]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- CXCR4 [Cycle 1, Day 5]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- CXCR4 [Cycle 1, Day 12]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- CXCR4 [Cycle 2, Day 1]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- CXCR4 [Cycle 2, Day 5]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- CXCR4 [Cycle 2, Day 12]
CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL)
- Hemoglobin F [Cycle 1, Day 1]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
- Hemoglobin F [Cycle 1, Day 5]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
- Hemoglobin F [Cycle 1, Day 12]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
- Hemoglobin F [Cycle 2, Day 1]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
- Hemoglobin F [Cycle 2, Day 5]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
- Hemoglobin F [Cycle 2, Day 12]
Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have histologically or cytologically confirmed myeloid metaplasia with myelofibrosis (this includes all subtypes - chronic idiopathic myelofibrosis or angiogenic myeloid metaplasia, post thrombocythemic and post polycythemic myelofibrosis); patients must have anemia (hemoglobin < 11 g/dL) or palpable splenomegaly (measured in cm from costal margin - to be eligible); patients with palpable splenomegaly must have spleen size documented ultrasonographically as well; they must also meet standard diagnostic criteria for MMM
-
Patients with morphologic evidence of advanced phases of the disease including accelerated (10-19% blasts) phase or with evidence of evolution to acute leukemia (>= 20% blasts) are also eligible for this study
-
The Italian Diagnostic Criteria for MMM
-
Necessary criteria
-
Diffuse bone marrow fibrosis
-
Absence of the Philadelphia chromosome or BCR-ABL rearrangement in peripheral blood cells
-
Optional criteria
-
Splenomegaly of any grade
-
Anisopoikilocytosis with tear drop erythrocytes
-
Presence of circulating immature myeloid cells
-
Presence of circulating erythroblasts
-
Presence of clusters of megakaryoblasts and anomalous megakaryocytes in bone marrow sections
-
Myeloid metaplasia
-
Diagnosis of MMM is acceptable if the following combinations are present
-
The two necessary criteria plus any other two optional criteria when splenomegaly is present OR
-
The two necessary criteria plus any other four optional criteria when splenomegaly is absent
-
Patients may have had prior chemotherapy or radiation therapy including splenic irradiation; prior therapy with erythropoietin, granulocyte-colony stimulating factor (GCSF), other growth factors or androgenic steroids is also permitted; there is no limit to the number of prior regimens received; at least 4 weeks must have elapsed since prior chemo or radiation therapy; at least 2 weeks must have elapsed since growth factor (erythropoietin, GCSF, granulocyte-macrophage colony-stimulating factor [GM-CSF]) or other therapy
-
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
-
Total bilirubin =< 2mg/dL
-
In patients with associated hemolytic anemia; total bilirubin > 2mg/dL is permissible as long as this is as a result of predominantly unconjugated hyperbilirubinemia; such patients may be enrolled only after discussion with the study chair
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal unless due to disease
-
Serum creatinine =< 2mg/dL
-
Patients must not be pregnant or nursing; women of child- bearing potential and men must agree to use an effective contraceptive method; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
-
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
-
Prior therapy with decitabine
-
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
-
Patients may not be receiving any other investigational agents
-
Patients with known central nervous system (CNS) disease should be excluded from this clinical trial
-
History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine
-
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
-
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with decitabine
-
Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
2 | Decatur Memorial Hospital | Decatur | Illinois | United States | 62526 |
3 | NorthShore University HealthSystem-Evanston Hospital | Evanston | Illinois | United States | 60201 |
4 | Ingalls Memorial Hospital | Harvey | Illinois | United States | 60426 |
5 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
6 | Illinois CancerCare-Peoria | Peoria | Illinois | United States | 61615 |
7 | Central Illinois Hematology Oncology Center | Springfield | Illinois | United States | 62702 |
8 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
9 | Fort Wayne Medical Oncology and Hematology Inc-Parkview | Fort Wayne | Indiana | United States | 46845 |
10 | Northern Indiana Cancer Research Consortium | South Bend | Indiana | United States | 46628 |
11 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
12 | Oncology Care Associates PLLC | Saint Joseph | Michigan | United States | 49085 |
13 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
14 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Olatoyosi M Odenike, University of Chicago Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2011-01444
- NCI-2011-01444
- CDR0000393839
- NCI-6814
- UCCRC-13327A
- 13327A
- 6814
- N01CM62201
- N01CM62207
- P30CA014599
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Decitabine |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Period Title: Overall Study | |
STARTED | 21 |
COMPLETED | 21 |
NOT COMPLETED | 0 |
Baseline Characteristics
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Overall Participants | 21 |
Age (years) [Median (Full Range) ] | |
Median (Full Range) [years] |
67
|
Sex: Female, Male (Count of Participants) | |
Female |
9
42.9%
|
Male |
12
57.1%
|
Region of Enrollment (participants) [Number] | |
United States |
21
100%
|
Outcome Measures
Title | Response Rate (Complete Response, Partial Response, or Hematologic Improvement. |
---|---|
Description | Complete response is normalization of counts and transfusion-independence. Partial response is hemoglobin increase to normal levels, multilineage improvement including absolute neutrophil count (ANC) and/or platelets. Hematologic improvement is red cell transfusion-independence or >50% increase in platelet levels. |
Time Frame | Up to 36 weeks (6 cycles) |
Outcome Measure Data
Analysis Population Description |
---|
Two patients were non-evaluable for response. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 19 |
Number (90% Confidence Interval) [percentage of participants] |
37
176.2%
|
Title | Incidence of Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0 |
---|---|
Description | Percentage of patients experiencing any toxicity, any grade level. Additional details on adverse events are reported in Adverse Events section. |
Time Frame | Up to 30 days of last dose of decitabine |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive decitabine subcutaneously on days 1-5 and 8-12. decitabine: Given SC |
Measure Participants | 21 |
Number (95% Confidence Interval) [percentage of patients] |
100
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 1, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
One patient had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 20 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
117
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 1, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
One patient had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 20 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
71
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 1, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Three patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 18 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
35
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 2, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
Five patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 16 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
76
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 2, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Six patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 15 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
35
|
Title | CD34+ Cells |
---|---|
Description | CD34 positive(+) cells are determined by flow immunostaining and light scatter in peripheral blood. Samples are then analyzed by flow cytometry, and CD34+ cells quantitated after 75,000 CD45 events are studied. (At least 75,000 CD45 events must be studied to ensure accuracy of the assay). Absolute numbers are determined by multiplying the % CD34+ cells by the total white blood cell count obtained on a CBC that is processed simultaneously. |
Time Frame | Cycle 2, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Six patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 15 |
Geometric Mean (95% Confidence Interval) [cells x 10^6/L] |
21
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Arm I |
---|---|---|
Comments | Mixed effects regression analysis of change over time in CD34+ cell levels. Analysis performed on log scale. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | 5 degrees of freedom test over six time points: day 1 (pre-treatment) and days 5, 12, 43, 47, and 54 post treatment. |
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 1, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
Four patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 17 |
Geometric Mean (95% Confidence Interval) [ratio] |
4.4
|
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 1, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Three patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 18 |
Geometric Mean (95% Confidence Interval) [ratio] |
5.7
|
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 1, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Three patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 18 |
Geometric Mean (95% Confidence Interval) [ratio] |
6.4
|
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 2, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
Seven patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 14 |
Geometric Mean (95% Confidence Interval) [ratio] |
4.0
|
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 2, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Seven patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 14 |
Geometric Mean (95% Confidence Interval) [ratio] |
6.0
|
Title | CXCR4 |
---|---|
Description | CXCR4 gene expression level measured by real-time RT_PCR. Ratio of CXCR4 vs a housekeeping gene (i.e., ABL) |
Time Frame | Cycle 2, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Eleven patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 10 |
Geometric Mean (95% Confidence Interval) [ratio] |
7.1
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Arm I |
---|---|---|
Comments | Mixed effects regression analysis of change over time in CXCR4 levels. Analysis performed on log scale. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.29 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | 5 degrees of freedom test over six time points: day 1 (pre-treatment) and days 5, 12, 43, 47, and 54 post treatment. |
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 1, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
Four patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 17 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.6
|
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 1, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Three patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 18 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.6
|
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 1, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Three patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 18 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.4
|
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 2, Day 1 |
Outcome Measure Data
Analysis Population Description |
---|
Nine patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 12 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.5
|
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 2, Day 5 |
Outcome Measure Data
Analysis Population Description |
---|
Seven patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 14 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.5
|
Title | Hemoglobin F |
---|---|
Description | Percentage of hemoglobin F as a proportion of total Hb (%HbF) measured by HPLC on peripheral blood samples. Midpoint of 0.5% imputed for values reported as below limit of detection (1.0%). Hemoglobin F has been previously shown to be upregulated by decitabine in other hematologic disorders- sickle cell disease specifically. The rationale for exploring it in this study was to evaluate its potential utility as a biomarker of drug effect/PD marker. |
Time Frame | Cycle 2, Day 12 |
Outcome Measure Data
Analysis Population Description |
---|
Seven patients had missing data. |
Arm/Group Title | Arm I |
---|---|
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC |
Measure Participants | 14 |
Mean (95% Confidence Interval) [percentage of HbF] |
1.5
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Arm I |
---|---|---|
Comments | Mixed effects regression analysis of change over time in hemoglobin F levels. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.99 |
Comments | ||
Method | Mixed Models Analysis | |
Comments | 5 degrees of freedom test over six time points: day 1 (pre-treatment) and days 5, 12, 43, 47, and 54 post treatment. |
Adverse Events
Time Frame | Up to 30 days of last dose of decitabine | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Arm I | |
Arm/Group Description | Patients receive 0.3 mg/kg/day decitabine subcutaneously on days 1-5 and 8-12. decitabine : Given SC | |
All Cause Mortality |
||
Arm I | ||
Affected / at Risk (%) | # Events | |
Total | / (NaN) | |
Serious Adverse Events |
||
Arm I | ||
Affected / at Risk (%) | # Events | |
Total | 15/21 (71.4%) | |
Blood and lymphatic system disorders | ||
Anemia | 4/21 (19%) | |
Febrile neutropenia | 8/21 (38.1%) | |
Gastrointestinal disorders | ||
Abdominal pain | 1/21 (4.8%) | |
Esophageal varices hemorrhage | 1/21 (4.8%) | |
Oesophageal varices | 1/21 (4.8%) | |
Vomiting | 1/21 (4.8%) | |
General disorders | ||
Sweet's Syndrome | 1/21 (4.8%) | |
Fever | 1/21 (4.8%) | |
General disorders and administration site conditions - Other | 1/21 (4.8%) | |
Infections and infestations | ||
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Blood | 3/21 (14.3%) | |
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Catheter-related | 1/21 (4.8%) | |
Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L): Lung (pneumonia) | 2/21 (9.5%) | |
Infections and infestations - Other | 4/21 (19%) | |
Lung infection | 1/21 (4.8%) | |
Investigations | ||
Neutrophil count decreased | 4/21 (19%) | |
Platelet count decreased | 3/21 (14.3%) | |
White blood cell decreased | 1/21 (4.8%) | |
Metabolism and nutrition disorders | ||
Hypoglycemia | 1/21 (4.8%) | |
Psychiatric disorders | ||
Confusion | 2/21 (9.5%) | |
Renal and urinary disorders | ||
Acute kidney injury | 1/21 (4.8%) | |
Urinary retention | 1/21 (4.8%) | |
Respiratory, thoracic and mediastinal disorders | ||
Dyspnea | 1/21 (4.8%) | |
Hypoxia | 1/21 (4.8%) | |
Vascular disorders | ||
Splenic infarct vs hemorrhage/rupture | 1/21 (4.8%) | |
Hematoma | 2/21 (9.5%) | |
Hypotension | 2/21 (9.5%) | |
Vascular disorders - Other | 1/21 (4.8%) | |
Other (Not Including Serious) Adverse Events |
||
Arm I | ||
Affected / at Risk (%) | # Events | |
Total | 19/21 (90.5%) | |
Blood and lymphatic system disorders | ||
Anemia | 16/21 (76.2%) | |
Febrile neutropenia | 7/21 (33.3%) | |
Gastrointestinal disorders | ||
Abdominal distension | 2/21 (9.5%) | |
Abdominal pain | 4/21 (19%) | |
Constipation | 7/21 (33.3%) | |
Diarrhea | 7/21 (33.3%) | |
Dysphagia | 2/21 (9.5%) | |
Mucositis oral | 5/21 (23.8%) | |
Nausea | 7/21 (33.3%) | |
Oral hemorrhage | 2/21 (9.5%) | |
Vomiting | 2/21 (9.5%) | |
General disorders | ||
Chills | 2/21 (9.5%) | |
Edema limbs | 5/21 (23.8%) | |
Fatigue | 14/21 (66.7%) | |
Fever | 4/21 (19%) | |
Injection site reaction | 2/21 (9.5%) | |
Infections and infestations | ||
Infections and infestations - Other | 5/21 (23.8%) | |
Injury, poisoning and procedural complications | ||
Bruising | 2/21 (9.5%) | |
Investigations | ||
Alanine aminotransferase increased | 6/21 (28.6%) | |
Alkaline phosphatase increased | 8/21 (38.1%) | |
Aspartate aminotransferase increased | 5/21 (23.8%) | |
Blood bilirubin increased | 6/21 (28.6%) | |
CD4 lymphocytes decreased | 2/21 (9.5%) | |
Creatinine increased | 5/21 (23.8%) | |
INR increased | 4/21 (19%) | |
Lymphocyte count decreased | 3/21 (14.3%) | |
Neutrophil count decreased | 15/21 (71.4%) | |
Platelet count decreased | 16/21 (76.2%) | |
Weight loss | 3/21 (14.3%) | |
White blood cell decreased | 17/21 (81%) | |
Metabolism and nutrition disorders | ||
Anorexia | 9/21 (42.9%) | |
Hypercalcemia | 2/21 (9.5%) | |
Hyperglycemia | 14/21 (66.7%) | |
Hyperkalemia | 5/21 (23.8%) | |
Hypermagnesemia | 3/21 (14.3%) | |
Hypoalbuminemia | 10/21 (47.6%) | |
Hypocalcemia | 11/21 (52.4%) | |
Hypokalemia | 4/21 (19%) | |
Hyponatremia | 6/21 (28.6%) | |
Hypophosphatemia | 4/21 (19%) | |
Musculoskeletal and connective tissue disorders | ||
Arthralgia | 3/21 (14.3%) | |
Bone pain | 2/21 (9.5%) | |
Generalized muscle weakness | 3/21 (14.3%) | |
Myalgia | 5/21 (23.8%) | |
Pain in extremity | 2/21 (9.5%) | |
Nervous system disorders | ||
Dizziness | 3/21 (14.3%) | |
Headache | 2/21 (9.5%) | |
Psychiatric disorders | ||
Insomnia | 2/21 (9.5%) | |
Renal and urinary disorders | ||
Proteinuria | 2/21 (9.5%) | |
Urinary frequency | 2/21 (9.5%) | |
Urinary retention | 2/21 (9.5%) | |
Respiratory, thoracic and mediastinal disorders | ||
Cough | 3/21 (14.3%) | |
Dyspnea | 5/21 (23.8%) | |
Pharyngolaryngeal pain | 4/21 (19%) | |
Skin and subcutaneous tissue disorders | ||
Hyperhidrosis | 3/21 (14.3%) | |
Rash maculo-papular | 5/21 (23.8%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Olatoyosi Odenike, MD |
---|---|
Organization | University of Chicago |
Phone | 773-702-3354 |
todenike@medicine.bsd.uchicago.edu |
- NCI-2011-01444
- NCI-2011-01444
- CDR0000393839
- NCI-6814
- UCCRC-13327A
- 13327A
- 6814
- N01CM62201
- N01CM62207
- P30CA014599