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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01350947
Recruitment Status : Completed
First Posted : May 10, 2011
Results First Posted : October 29, 2015
Last Update Posted : June 13, 2016
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
University of Utah

Tracking Information
First Submitted Date  ICMJE April 29, 2011
First Posted Date  ICMJE May 10, 2011
Results First Submitted Date  ICMJE September 28, 2015
Results First Posted Date  ICMJE October 29, 2015
Last Update Posted Date June 13, 2016
Study Start Date  ICMJE April 2011
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
Percentage of Patients With Complete Hematologic Response (According to IWG 2006 Criteria) in CMML Patients Treated With 5-azacitidine. [ Time Frame: 24 months ]
Complete Hematologic Response is defined as: bone marrow evaluation shows <= 5% myeloblasts with normal maturation of all cells lines; peripheral blood evaluation shows hemoglobin >= 11 g/dL, neutrophils >= 1000/mL, platelets >= 100,000/mL, 0% blasts
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2011)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2011)
  • • To determine the rate of complete and partial cytogenetic response to 5-azacitidine in CMML patients with clonal chromosomal abnormalities. [ Time Frame: 24 months ]
  • • To determine the rate of overall and progression free survival at 24 months in CMML subjects treated with 5-azacitidine [ Time Frame: 24 months ]
  • • To determine the frequency of known leukemia-associated mutations in the population under study. [ Time Frame: 48 months ]
  • • 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 ]
  • • 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 ]
  • • To develop biomarkers of response to 5-azacitidine. [ Time Frame: 48 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
Official Title  ICMJE A Phase II Study of the Efficacy, Safety and Determinants of Response to 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia (CMML)
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Myelomonocytic Leukemia
Intervention  ICMJE 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®
Study Arms  ICMJE Experimental: All patients
All participants enrolled.
Intervention: Drug: 5-Azacitidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 28, 2014)
11
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2011)
50
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01350947
Other Study ID Numbers  ICMJE HCI47081
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Celgene
Investigators  ICMJE
Principal Investigator: Michael Deininger, MD University of Utah
PRS Account University of Utah
Verification Date May 2016

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