A Study of 5-Azacitidine (Vidaza®) in Patients With Chronic Myelomonocytic Leukemia
Condition: Chronic Myelomonocytic Leukemia
MeSH terms: Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
Intervention: 5-Azacitidine
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.
Intervention MeSH terms: Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Myelomonocytic Leukemia; CMML

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.
    

Eligibility criteria:

        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)