Clinical Trial: Decitabine in Treating Patients With Myelofibrosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase II Study of Decitabine in Myelofibrosis

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.

Detailed Summary:

PRIMARY OBJECTIVES:

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

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

SECONDARY OBJECTIVES:

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

II. 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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Response Rate (Complete Response, Partial Response, or Hematologic Improvement. [ Time Frame: 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 [ Time Frame: 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.


Original Primary Outcome:

Current Secondary Outcome:

  • CD34+ Cells [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Cycle 1, Day 5 ]

    Percentage of hemoglobin F as a prop

    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: November 9, 2004
    Date Started: September 2004
    Date Completion:
    Last Updated: March 3, 2017
    Last Verified: December 2016