Decitabine in Treating Patients With Myelofibrosis

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Active, not recruiting
CT.gov ID
NCT00095784
Collaborator
(none)
21
14
1
1.5

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:
  1. To determine response rate (complete and partial responses and hematological improvement) to decitabine in patients with myelofibrosis.

  2. To determine the safety of decitabine in patients with myelofibrosis.

SECONDARY OBJECTIVES:
  1. To determine the effects of decitabine on specific epigenetic changes including methylation status of specific target genes and gene re-expression.

  2. 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

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Decitabine in Myelofibrosis
Actual Study Start Date :
Sep 29, 2004
Actual Primary Completion Date :
Jul 1, 2008

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:
  • 5-Aza-2'-deoxycytidine
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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)

    8. 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)

    9. 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)

    10. 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)

    11. 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)

    12. 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)

    13. 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.

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00095784
    Other Study ID Numbers:
    • NCI-2011-01444
    • NCI-2011-01444
    • CDR0000393839
    • NCI-6814
    • UCCRC-13327A
    • 13327A
    • 6814
    • N01CM62201
    • N01CM62207
    • P30CA014599
    First Posted:
    Nov 9, 2004
    Last Update Posted:
    Jun 29, 2022
    Last Verified:
    Jun 1, 2022
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Primary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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
    6. Secondary Outcome
    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
    7. Secondary Outcome
    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
    8. Secondary Outcome
    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.
    9. Secondary Outcome
    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
    10. Secondary Outcome
    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
    11. Secondary Outcome
    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
    12. Secondary Outcome
    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
    13. Secondary Outcome
    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
    14. Secondary Outcome
    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.
    15. Secondary Outcome
    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
    16. Secondary Outcome
    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
    17. Secondary Outcome
    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
    18. Secondary Outcome
    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
    19. Secondary Outcome
    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
    20. Secondary Outcome
    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

    [Not Specified]

    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
    Email todenike@medicine.bsd.uchicago.edu
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00095784
    Other Study ID Numbers:
    • NCI-2011-01444
    • NCI-2011-01444
    • CDR0000393839
    • NCI-6814
    • UCCRC-13327A
    • 13327A
    • 6814
    • N01CM62201
    • N01CM62207
    • P30CA014599
    First Posted:
    Nov 9, 2004
    Last Update Posted:
    Jun 29, 2022
    Last Verified:
    Jun 1, 2022