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

• 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: University of Utah
• Collaborator: Celgene
• Information provided by (Responsible Party): University of Utah

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.

Condition or disease	Intervention/treatment	Phase
Chronic Myelomonocytic Leukemia	Drug: 5-Azacitidine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: April 2011
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: September 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: All patients; All participants enrolled.

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®

Outcome Measures

Primary Outcome Measures :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, New York

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Utah

Celgene

Investigators

• Principal Investigator: Michael Deininger, MD; University of Utah

More Information

• Responsible Party: University of Utah
• ClinicalTrials.gov Identifier: NCT01350947
• Other Study ID Numbers: HCI47081
• First Posted: May 10, 2011
• Results First Posted: October 29, 2015
• Last Update Posted: June 13, 2016
• Last Verified: May 2016

Keywords provided by University of Utah:

Chronic Myelomonocytic Leukemia; CMML

Additional relevant MeSH terms:

Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Azacitidine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors