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

• Sponsor: University of Utah (Other)
• Overall Status: Completed
• CT.gov ID: NCT01350947
• Collaborator: Celgene (Industry)
• Enrollment: 11
• Locations: 3
• Arm: 1
• Duration (Months): 41
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Apr 1, 2011
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 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 Names: 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. [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of CMML as defined by the WHO criteria

2. Persistent peripheral blood monocytosis of more than 1 x 109/L for at least 3 months and

3. No Philadelphia chromosome or BCR-ABL fusion gene and

4. Less than 20% blasts in the blood or bone marrow and

5. 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.

6. Age of 18 years or older. Both men and women and members of all races and ethnic groups will be included.

7. ECOG performance status <3

8. Adequate organ function defined as:

9. Total bilirubin <2.5 x upper limit of normal (ULN)

10. Direct bilirubin <2 x ULN

11. Creatinine <2 mg/dL

12. ALT and AST <2.5 x ULN

13. Ability to understand and the willingness to sign a written informed consent document

14. 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

	Site	City	State	Country	Postal Code
1	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
2	Oregon Health and Science University	Portland	Oregon	United States	97239
3	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Utah
• ClinicalTrials.gov Identifier: NCT01350947
• Other Study ID Numbers: HCI47081
• First Posted: May 10, 2011
• Last Update Posted: Jun 13, 2016
• Last Verified: May 1, 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; Azacitidine

Study Results

Participant Flow

Arm/Group Title	Arm 1 - 5-Azacitidine
Arm/Group Description	All participants enrolled. 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.
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Patients
Arm/Group Description	All participants enrolled. 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.
Overall Participants	11
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	5 45.5%
Male	6 54.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Complete Hematologic Response (According to IWG 2006 Criteria) in CMML Patients Treated With 5-azacitidine.
Description	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
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1 - 5-Azacitidine
Arm/Group Description	All participants enrolled. 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.
Measure Participants	11
Number [percentage of patients]	27

Adverse Events

Arm/Group Title	Arm 1 - 5-Azacitidine
Arm/Group Description	All participants enrolled. 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.
All Cause Mortality
	Arm 1 - 5-Azacitidine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Arm 1 - 5-Azacitidine
	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)
Blood and lymphatic system disorders
leukocytosis	1/11 (9.1%)	1
Hematochezia	1/11 (9.1%)	1
Gastrointestinal disorders
Mucositis	1/11 (9.1%)	1
General disorders
Fatigue	1/11 (9.1%)	1
wound treatment	1/11 (9.1%)	1
Investigations
Thrombocytopenia	1/11 (9.1%)	1
Nervous system disorders
seizure	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Arm 1 - 5-Azacitidine
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anemia	7/11 (63.6%)	22
bloody discharge from urethra	1/11 (9.1%)	1
Hematochezia	1/11 (9.1%)	1
leucocytosis	1/11 (9.1%)	1
neutropenic fever	1/11 (9.1%)	2
Cardiac disorders
Occasional palpitations	1/11 (9.1%)	1
tachycardia	1/11 (9.1%)	1
Ear and labyrinth disorders
labyrinthitis	1/11 (9.1%)	1
ear lesion	1/11 (9.1%)	1
Eye disorders
Broken Blood Vessel of the Eye	1/11 (9.1%)	1
eye irratation	1/11 (9.1%)	1
eye swelling	1/11 (9.1%)	1
Gastrointestinal disorders
Abdominal Cramping	2/11 (18.2%)	2
abdominal pain	2/11 (18.2%)	2
bloating	1/11 (9.1%)	1
Constipation	9/11 (81.8%)	10
Diarrhea	3/11 (27.3%)	3
dry mouth	1/11 (9.1%)	1
dyspepsia	1/11 (9.1%)	1
dysphagia	1/11 (9.1%)	1
epigastric pain	1/11 (9.1%)	1
loose stool	1/11 (9.1%)	1
mouth sores	1/11 (9.1%)	1
Nausea	6/11 (54.5%)	11
oral herpes lesion	1/11 (9.1%)	1
stomach pain	1/11 (9.1%)	1
tooth pain	1/11 (9.1%)	1
Vomiting	3/11 (27.3%)	3
General disorders
chest pain	1/11 (9.1%)	1
chills	1/11 (9.1%)	1
cold sweats	1/11 (9.1%)	1
cold symptoms	1/11 (9.1%)	1
Cooler Lower Extremeties	1/11 (9.1%)	1
dry nose	1/11 (9.1%)	1
Fatigue	5/11 (45.5%)	5
flu like symptoms	2/11 (18.2%)	2
injection reaction	3/11 (27.3%)	5
malaise	2/11 (18.2%)	2
Night Sweats	2/11 (18.2%)	2
Nightmares	1/11 (9.1%)	1
Nose Sore	1/11 (9.1%)	1
wound treatment	1/11 (9.1%)	1
Infections and infestations
Bacteremia	1/11 (9.1%)	1
cellulitis	2/11 (18.2%)	2
port site infection	1/11 (9.1%)	1
Rhinitis	1/11 (9.1%)	1
rhinovirus	1/11 (9.1%)	1
Urinary Tract Infection	1/11 (9.1%)	1
viral conjunctivitis	1/11 (9.1%)	1
Injury, poisoning and procedural complications
ankle sprain	1/11 (9.1%)	1
chest lesion	1/11 (9.1%)	1
Fall	3/11 (27.3%)	4
hip pain	1/11 (9.1%)	1
laceration	2/11 (18.2%)	3
scalp lesions	1/11 (9.1%)	1
shin lesion	1/11 (9.1%)	1
Sinus Infection	2/11 (18.2%)	2
Investigations
decreased neutrophil	1/11 (9.1%)	1
increased creatinine	1/11 (9.1%)	1
Leukopenia	7/11 (63.6%)	26
Thrombocytopenia	6/11 (54.5%)	40
tooth infection	1/11 (9.1%)	1
Weight Gain	1/11 (9.1%)	1
Metabolism and nutrition disorders
anorexia	2/11 (18.2%)	2
back pain	2/11 (18.2%)	3
Dehydration	1/11 (9.1%)	1
hyperglycema	1/11 (9.1%)	1
Hypomagnesemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
anthralgia	3/11 (27.3%)	3
bone pain	1/11 (9.1%)	1
flank pain	2/11 (18.2%)	2
foot edema	1/11 (9.1%)	1
leg pain	1/11 (9.1%)	2
limited movement of limb	1/11 (9.1%)	1
Muscle Cramps	1/11 (9.1%)	1
muscle weakness	1/11 (9.1%)	1
tendinitis	1/11 (9.1%)	1
torn ligament	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
chloroma	1/11 (9.1%)	1
parovaria cyst	1/11 (9.1%)	1
Nervous system disorders
Dizziness	3/11 (27.3%)	3
Dysgeusia	3/11 (27.3%)	4
headache	2/11 (18.2%)	2
neuropathy	1/11 (9.1%)	3
neutropenia	7/11 (63.6%)	59
seizures	1/11 (9.1%)	1
syncope	1/11 (9.1%)	2
tremor	1/11 (9.1%)	1
Psychiatric disorders
Depression	3/11 (27.3%)	4
insomnia	1/11 (9.1%)	1
Renal and urinary disorders
frequent urination	1/11 (9.1%)	1
Prostatitis	1/11 (9.1%)	1
Reproductive system and breast disorders
pelvic pain	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Cough	3/11 (27.3%)	3
dyspnea	3/11 (27.3%)	3
Epistaxis	3/11 (27.3%)	4
Hemoptysis	1/11 (9.1%)	1
Hypoxia	1/11 (9.1%)	1
Nasal Congestion	1/11 (9.1%)	1
Pneumonia	1/11 (9.1%)	1
Sleep apnea	1/11 (9.1%)	1
sore throat	1/11 (9.1%)	1
Upper Respiratory Infection	2/11 (18.2%)	2
Skin and subcutaneous tissue disorders
bruising	4/11 (36.4%)	4
dermatitis	1/11 (9.1%)	1
Ecchymoses	2/11 (18.2%)	3
erythmea	1/11 (9.1%)	1
face burning	1/11 (9.1%)	1
itching	1/11 (9.1%)	1
rash	2/11 (18.2%)	3
Vascular disorders
hematoma	3/11 (27.3%)	3
Hot Flashes	1/11 (9.1%)	1
hypotension	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.