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

Tracking Information

• First Submitted Date: April 29, 2011
• First Posted Date: May 10, 2011
• Results First Submitted Date: September 28, 2015
• Results First Posted Date: October 29, 2015
• Last Update Posted Date: June 13, 2016
• Study Start Date: April 2011
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2016)

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

• Original Primary Outcome Measures (submitted: May 9, 2011): To determine the rate of complete hematologic response and hematologic improvement (according to IWG 2006 criteria) in CMML patients treated with 5-azacitidine. [ Time Frame: 24 months ]
• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: May 9, 2011)

• • To determine the rate of complete and partial cytogenetic response to 5-azacitidine in CMML patients with clonal chromosomal abnormalities. [ Time Frame: 24 months ]
• • To determine the rate of overall and progression free survival at 24 months in CMML subjects treated with 5-azacitidine [ Time Frame: 24 months ]
• • To determine the frequency of known leukemia-associated mutations in the population under study. [ Time Frame: 48 months ]
• • To screen for genetic losses and gains in CMML cells compared to non-leukemic control cells from the same patient, using high density SNP array analysis. [ Time Frame: 48 months ]
• • To determine the gene expression profile and promoter methylation profile of CMML cells prior to and on therapy with 5-azacitidine. [ Time Frame: 48 months ]
• • To develop biomarkers of response to 5-azacitidine. [ Time Frame: 48 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Myelomonocytic Leukemia

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.

Other Name: Vidaza®

Study Arms

Experimental: All patients

All participants enrolled.

Intervention: Drug: 5-Azacitidine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 28, 2014): 11
• Original Estimated Enrollment (submitted: May 9, 2011): 50
• Actual Study Completion Date: September 2014
• Actual Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01350947
• Other Study ID Numbers: HCI47081
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Utah
• Study Sponsor: University of Utah
• Collaborators: Celgene

Investigators

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

• PRS Account: University of Utah
• Verification Date: May 2016