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

Chronic Myelomonocytic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01350947
• Other study ID #: HCI47081
• Status: Completed
• Phase: Phase 2
• First received: April 29, 2011
• Last updated: September 28, 2015
• Start date: April 2011
• Est. completion date: September 2014

Study information

• Verified date: September 2015
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Utah	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To Determine the Rate of Complete Hematologic Response (According to IWG 2006 Criteria) in CMML Patients Treated With 5-azacitidine.		24 months	No