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A Phase II Study of the Efficacy, Safety and Determinants of Response to 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia (CMML)

Phase 2
18 Years
Open (Enrolling)
Chronic Myelomonocytic Leukemia

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Trial Information

A Phase II Study of the Efficacy, Safety and Determinants of Response to 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia (CMML)

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

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.

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

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)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Time Frame:

24 months

Safety Issue:


Principal Investigator

Michael Deininger, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Utah


United States: Institutional Review Board

Study ID:




Start Date:

April 2011

Completion Date:

December 2013

Related Keywords:

  • Chronic Myelomonocytic Leukemia
  • Chronic Myelomonocytic Leukemia
  • CMML
  • Leukemia
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Myelomonocytic, Acute



Roswell Park Cancer Institute Buffalo, New York  14263
University of Utah Salt Lake City, Utah  
Oregon Health and Science University Portland, Oregon  97201