A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
Primary Purpose
Chronic Myelomonocytic Leukemia
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
5-Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelomonocytic Leukemia focused on measuring Chronic Myelomonocytic Leukemia, CMML
Eligibility Criteria
Inclusion Criteria:
Diagnosis of CMML as defined by the WHO criteria
- Persistent peripheral blood monocytosis of more than 1 x 109/L for at least 3 months and
- No Philadelphia chromosome or BCR-ABL fusion gene and
- Less than 20% blasts in the blood or bone marrow and
- 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.
- Age of 18 years or older. Both men and women and members of all races and ethnic groups will be included.
- ECOG performance status <3
Adequate organ function defined as:
- Total bilirubin <2.5 x upper limit of normal (ULN)
- Direct bilirubin <2 x ULN
- Creatinine <2 mg/dL
- ALT and AST <2.5 x ULN
- Ability to understand and the willingness to sign a written informed consent document
- Willingness to use adequate contraception for the duration of the study
Exclusion Criteria:
- 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.
- 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)
- Known or suspected hypersensitivity to 5-azacitidine or mannitol
- 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
- Major surgery within 28 days before registration (exception: central venous line placement), or lack of full recovery from prior major surgery
- Prior therapy with a hypomethylating agent
- Cytotoxic chemotherapy less than 2 weeks prior to starting study medication (exception: hydroxyurea and/or anagrelide)
- Erythropoietin or darbepoietin, G-CSF, GM-CSF, thalidomide or lenalidomide less than 2 weeks from day 1 of cycle 1
- Concomitant cytotoxic chemotherapy (exception: hydroxyurea for up to 1 week per cycle)
- Concomitant therapy with other investigational agents
- Other active malignancies except basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- Pregnancy or breastfeeding (possible risk to the fetus or infant)
Sites / Locations
- Roswell Park Cancer Institute
- Oregon Health and Science University
- University of Utah
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All patients
Arm Description
All participants enrolled.
Outcomes
Primary Outcome Measures
Percentage of Patients With Complete Hematologic Response (According to IWG 2006 Criteria) in CMML Patients Treated With 5-azacitidine.
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
Secondary Outcome Measures
Full Information
NCT ID
NCT01350947
First Posted
April 29, 2011
Last Updated
May 10, 2016
Sponsor
University of Utah
Collaborators
Celgene
1. Study Identification
Unique Protocol Identification Number
NCT01350947
Brief Title
A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
Official Title
A Phase II Study of the Efficacy, Safety and Determinants of Response to 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia (CMML)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
September 2014 (Actual)
Study Completion Date
September 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Utah
Collaborators
Celgene
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelomonocytic Leukemia
Keywords
Chronic Myelomonocytic Leukemia, CMML
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
All patients
Arm Type
Experimental
Arm Description
All participants enrolled.
Intervention Type
Drug
Intervention Name(s)
5-Azacitidine
Other Intervention Name(s)
Vidaza®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Patients With Complete Hematologic Response (According to IWG 2006 Criteria) in CMML Patients Treated With 5-azacitidine.
Description
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
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of CMML as defined by the WHO criteria
Persistent peripheral blood monocytosis of more than 1 x 109/L for at least 3 months and
No Philadelphia chromosome or BCR-ABL fusion gene and
Less than 20% blasts in the blood or bone marrow and
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.
Age of 18 years or older. Both men and women and members of all races and ethnic groups will be included.
ECOG performance status <3
Adequate organ function defined as:
Total bilirubin <2.5 x upper limit of normal (ULN)
Direct bilirubin <2 x ULN
Creatinine <2 mg/dL
ALT and AST <2.5 x ULN
Ability to understand and the willingness to sign a written informed consent document
Willingness to use adequate contraception for the duration of the study
Exclusion Criteria:
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.
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)
Known or suspected hypersensitivity to 5-azacitidine or mannitol
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
Major surgery within 28 days before registration (exception: central venous line placement), or lack of full recovery from prior major surgery
Prior therapy with a hypomethylating agent
Cytotoxic chemotherapy less than 2 weeks prior to starting study medication (exception: hydroxyurea and/or anagrelide)
Erythropoietin or darbepoietin, G-CSF, GM-CSF, thalidomide or lenalidomide less than 2 weeks from day 1 of cycle 1
Concomitant cytotoxic chemotherapy (exception: hydroxyurea for up to 1 week per cycle)
Concomitant therapy with other investigational agents
Other active malignancies except basal cell carcinoma of the skin and carcinoma in situ of the cervix.
Pregnancy or breastfeeding (possible risk to the fetus or infant)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Deininger, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
We'll reach out to this number within 24 hrs