Clinical trial NCT00095784: Decitabine in Treating Patients With Myelofibrosis
Official title: A Phase II Study of Decitabine in Myelofibrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Primary Myelofibrosis
Secondary Myelofibrosis
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-11-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 description: 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.

Eligibility 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

Primary outcomes:
measure: Response Rate (Complete Response, Partial Response, or Hematologic Improvement.
timeFrame: Up to 36 weeks (6 cycles)
measure: Incidence of Toxicities, Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
timeFrame: Up to 30 days of last dose of decitabine
Secondary outcomes:
measure: CD34+ Cells
timeFrame: Cycle 1, Day 1
measure: CD34+ Cells
timeFrame: Cycle 1, Day 5
measure: CD34+ Cells
timeFrame: Cycle 1, Day 12
measure: CD34+ Cells
timeFrame: Cycle 2, Day 1
measure: CD34+ Cells
timeFrame: Cycle 2, Day 5
measure: CD34+ Cells
timeFrame: Cycle 2, Day 12
measure: CXCR4
timeFrame: Cycle 1, Day 1
measure: CXCR4
timeFrame: Cycle 1, Day 5
measure: CXCR4
timeFrame: Cycle 1, Day 12
measure: CXCR4
timeFrame: Cycle 2, Day 1
measure: CXCR4
timeFrame: Cycle 2, Day 5
measure: CXCR4
timeFrame: Cycle 2, Day 12
measure: Hemoglobin F
timeFrame: Cycle 1, Day 1
measure: Hemoglobin F
timeFrame: Cycle 1, Day 5
measure: Hemoglobin F
timeFrame: Cycle 1, Day 12
measure: Hemoglobin F
timeFrame: Cycle 2, Day 1
measure: Hemoglobin F
timeFrame: Cycle 2, Day 5
measure: Hemoglobin F
timeFrame: Cycle 2, Day 12
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Saint Joseph
country: United States
facility: Oncology Care Associates PLLC
state: Michigan
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Olatoyosi M Odenike
role: PRINCIPAL_INVESTIGATOR
References: