Ph II Study of Azacitidine in Myelofibrosis

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00569660
• Collaborator: Celgene Corporation (Industry)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 34
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if azacitidine can help to control MF. The safety of azacitidine in patients with Myelofibrosis (MF) will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis	Drug: Azacitidine	Phase 2

Detailed Description

Azacitidine is a drug that is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the "bad" genes, the tumor-fighting genes may be able to work better.

If you are found to be eligible to take part in this study, you will be able to begin treatment with azacitidine. You will receive azacitidine as an injection under the skin once a day for 7 days in a row. This will be repeated every 4 weeks (4 weeks equals 1 cycle). The first cycle of azacitidine will be given at M. D. Anderson, in an outpatient setting. Later cycles of treatment courses may be given at M. D. Anderson or by a cancer doctor in your community.

You may receive up to 12 cycles of treatment if you are responding well to treatment. You will be taken off study if your disease gets worse or intolerable side effects occur. Once you go off study, you will receive follow-up as is standard of care for your disease.

This is an investigational study. Azacitidine is FDA approved for the treatment of myelodysplastic syndrome. Its use in this study is experimental. A total of up to 34 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Azacitidine in Myelofibrosis
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azacitidine 75 mg/m^2 Subcutaneous Daily for 7 days every 4 weeks	Drug: Azacitidine; 75 mg/m^2 subcutaneous daily for 7 days (every 4 week cycle); Other Names: Vidaza

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Clinical Response [Every 2 courses of 4 week therapy = each 8 weeks]

   Objective Clinical Response includes Participants with Complete Response, Partial Response or Hematologic Improvement and No Response. Bone marrow aspiration and biopsy with cytogenetics every 2 to 4 courses.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of MF requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to Lille scoring system (adverse prognostic factors are: Hemoglobin (Hb) < 10 g/dl, White Blood Cell (WBC) < 4 or > 30 x 10*9/L; risk group: 0 = low, 1 = intermediate, 2 = high).

• Performance 0-2 Eastern Cooperative Oncology Group (ECOG).

• Signed informed consent.

• Patients must have been off chemotherapy for 2 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy. Patients are allowed to be on anagrelide and hydroxyurea to control high platelet and WBC counts for their safety.

• Serum bilirubin levels </= 1.5 times the upper limit of the normal range for the laboratory Upper Limit of of Normal(ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis.

• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels </= 2 x ULN.

• Serum creatinine levels </= 1.5 x ULN; unless related to the MF, as judged by treating physicians.

• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine treatment and should be advised to avoid becoming pregnant. Men must be advised to not father a child while receiving treatment with azacitidine. Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures).

• Age >/= 18.

Exclusion Criteria:

• Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

• Uncontrolled intercurrent illness including, but not limited to, uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

• Known or suspected hypersensitivity to azacitidine or mannitol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Celgene Corporation

Investigators

• Principal Investigator: Srdan Verstovsek, M.D., M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson's Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00569660
• Other Study ID Numbers: 2005-0033
• First Posted: Dec 7, 2007
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Myelofibrosis; MF; Leukemia; Azacitidine; Vidaza
• Additional relevant MeSH terms: Primary Myelofibrosis; Azacitidine

Study Results

Participant Flow

Recruitment Details	Recruitment Period 6/7/05 to 4/4/08. All patients registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment Detail	The maximum accrual of 34 was met.

Arm/Group Title	Azacitidine
Arm/Group Description	75 mg/m^2 Subcutaneous daily for 7 days every 4 weeks
Period Title: Overall Study
STARTED	34
COMPLETED	34
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Azacitidine
Arm/Group Description	75 mg/m^2 Subcutaneous daily for 7 days every 4 weeks
Overall Participants	34
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 35.3%
>=65 years	22 64.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	12 35.3%
Male	22 64.7%
Region of Enrollment (participants) [Number]
United States	34 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Clinical Response
Description	Objective Clinical Response includes Participants with Complete Response, Partial Response or Hematologic Improvement and No Response. Bone marrow aspiration and biopsy with cytogenetics every 2 to 4 courses.
Time Frame	Every 2 courses of 4 week therapy = each 8 weeks

Outcome Measure Data

Analysis Population Description

The statistical analysis for response rates determined on the intent-to-treat (ITT) populations. This is defined as all enrolled patients who received at least one dose of study medication.

Arm/Group Title	Azacitidine
Arm/Group Description	75 mg/m^2 Subcutaneous daily for 7 days every 4 weeks
Measure Participants	34
Complete Response	0 0%
Partial Response	1 2.9%
Hematologic Improvement	7 20.6%
No Response	26 76.5%

Adverse Events

Time Frame	2 years 9 months
Arm/Group Title	Azacitidine
Arm/Group Description	75 mg/m^2 Subcutaneous daily for 7 days every 4 weeks
All Cause Mortality
	Azacitidine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Azacitidine
	Affected / at Risk (%)	# Events
Total	17/34 (50%)
Blood and lymphatic system disorders
Hyperuricemia	2/34 (5.9%)	2
Neutropenia Without Fever	2/34 (5.9%)	2
Cardiac disorders
CNS Cerebrovascular Ischema	1/34 (2.9%)	1
Aortic Aneurism	1/34 (2.9%)	1
Gastrointestinal disorders
Nausea	3/34 (8.8%)	3
Vomiting	3/34 (8.8%)	3
General disorders
Edema	1/34 (2.9%)	1
Infections and infestations
Infection soft tissue	1/34 (2.9%)	1
Neutropenic Fever	2/34 (5.9%)	2
Pneumonia	3/34 (8.8%)	3
Non-Neutropenic Fever	2/34 (5.9%)	2
Septic Arthritis Knee	1/34 (2.9%)	1
Bladder Infection	1/34 (2.9%)	1
Urosepsis Infection	1/34 (2.9%)	1
Infection Laceration Knee	1/34 (2.9%)	1
Gastrointestinal Infections	1/34 (2.9%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/34 (2.9%)	1
Skin and subcutaneous tissue disorders
Skin Desquamation	1/34 (2.9%)	1
Vascular disorders
Neurology Intracranial Bleed	1/34 (2.9%)	1
Superficial Thrombosis	1/34 (2.9%)	1
Hemorrhage Post Surgical	1/34 (2.9%)	1
Gastrointestinal Hemorrhage	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Azacitidine
	Affected / at Risk (%)	# Events
Total	10/34 (29.4%)
Blood and lymphatic system disorders
Neutropenia	10/34 (29.4%)	10
Renal and urinary disorders
Acute Renal Failure	2/34 (5.9%)	2

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.