A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT01350947
First received: April 29, 2011
Last updated: January 23, 2014
Last verified: January 2014

April 29, 2011
January 23, 2014
April 2011
June 2014   (final data collection date for primary outcome measure)
To determine the rate of complete hematologic response and hematologic improvement (according to IWG 2006 criteria) in CMML patients treated with 5-azacitidine. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01350947 on ClinicalTrials.gov Archive Site
  • • To determine the rate of complete and partial cytogenetic response to 5-azacitidine in CMML patients with clonal chromosomal abnormalities. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • • To determine the rate of overall and progression free survival at 24 months in CMML subjects treated with 5-azacitidine [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • • To determine the frequency of known leukemia-associated mutations in the population under study. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • • To screen for genetic losses and gains in CMML cells compared to non-leukemic control cells from the same patient, using high density SNP array analysis. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • • To determine the gene expression profile and promoter methylation profile of CMML cells prior to and on therapy with 5-azacitidine. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • • To develop biomarkers of response to 5-azacitidine. [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
A Phase II Study of the Efficacy, Safety and Determinants of Response to 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia (CMML)

The primary objective of this study is:

Response to treatment will be evaluated according to the revised International Working Group (IWG) categories natural history, hematologic improvement and cytogenetic response1;2. The primary objective is:

To determine the rate of complete hematologic response and hematologic improvement (according to IWG 2006 criteria) in CMML patients treated with 5-azacitidine.

In this study, eligible patients with a confirmed diagnosis of CMML will be treated with 5-azacitidine to determine the rates of complete hematologic response, hematologic improvement, complete and partial cytogenetic response, and overall and progression free survival.

To develop biomarkers associated with response and gain insights into the mechanisms that determine response, gene expression profiling, genome-wide SNP array analysis, microRNA analysis, and DNA methylation analysis will be performed prior to therapy and at defined time points during the study. Phosphoproteomics profiling may be included in the analysis.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Myelomonocytic Leukemia
Drug: 5-Azacitidine

Administered on Days 1-7 of each Cycle.

Subcutaneous administration:

To provide a homogeneous suspension, the contents of the syringe must be re-suspended by inverting the syringe 2-3 times and vigorously rolling the syringe between the palms for 30 seconds immediately prior to administration.

The 5-azacitidine suspension is administered subcutaneously.

Intravenous Administration:

5-Azacitidine solution is administered intravenously. Administer the total dose over a period of 10-40 minutes.

Other Name: Vidaza®
Experimental: All patients
All participants enrolled.
Intervention: Drug: 5-Azacitidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
June 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Diagnosis of CMML as defined by the WHO criteria

    1. Persistent peripheral blood monocytosis of more than 1 x 109/L for at least 3 months and
    2. No Philadelphia chromosome or BCR-ABL fusion gene and
    3. Less than 20% blasts in the blood or bone marrow and
    4. Dysplasia in one or more of the myeloid lineages* * In the absence of dysplasia in one or more of the myeloid lineages, the diagnosis of CMML can still be made if a) - c) are met AND an acquired clonal chromosomal abnormality is present in the bone marrow cells, the monocytosis has been present for more than 3months AND all other causes of monocytosis have been ruled out.
  2. Age of 18 years or older. Both men and women and members of all races and ethnic groups will be included.
  3. ECOG performance status <3
  4. Adequate organ function defined as:

    1. Total bilirubin <2.5 x upper limit of normal (ULN)
    2. Direct bilirubin <2 x ULN
    3. Creatinine <2 mg/dL
    4. ALT and AST <2.5 x ULN
  5. Ability to understand and the willingness to sign a written informed consent document
  6. Willingness to use adequate contraception for the duration of the study

Exclusion Criteria:

  1. Progression to acute myeloid leukemia (defined by at least 20% blasts in the blood or bone marrow). In the unlikely event that progression to acute leukemia is demonstrated in the "screening" bone marrow biopsy, it is at the discretion of the investigator to enroll the patient after adequate discussion of the findings and alternative therapies. Enrollment of such a patient must be reported to the HCI PI.
  2. Presence of activating mutations of the platelet derived growth factor receptors alpha or beta, which would suggest likely benefit from imatinib treatment (these mutations will usually be obvious from karyotyping and fluorescence in situ hybridization studies)
  3. Known or suspected hypersensitivity to 5-azacitidine or mannitol
  4. Clinically significant heart disease (New York Heart Association Class III or IV) or other serious intercurrent illnesses or psychiatric illness/social situations that would limit compliance with study requirements
  5. Major surgery within 28 days before registration (exception: central venous line placement), or lack of full recovery from prior major surgery
  6. Prior therapy with a hypomethylating agent
  7. Cytotoxic chemotherapy less than 2 weeks prior to starting study medication (exception: hydroxyurea and/or anagrelide)
  8. Erythropoietin or darbepoietin, G-CSF, GM-CSF, thalidomide or lenalidomide less than 2 weeks from day 1 of cycle 1
  9. Concomitant cytotoxic chemotherapy (exception: hydroxyurea for up to 1 week per cycle)
  10. Concomitant therapy with other investigational agents
  11. Other active malignancies except basal cell carcinoma of the skin and carcinoma in situ of the cervix.
  12. Pregnancy or breastfeeding (possible risk to the fetus or infant)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01350947
HCI47081
Yes
University of Utah
University of Utah
Celgene Corporation
Principal Investigator: Michael Deininger, MD University of Utah
University of Utah
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP