A Phase II Study of Intravenous Azacitidine Alone in Patients With Myelodysplastic Syndromes

NCT ID: NCT00384956

Last Updated: 2016-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2010-03-31

Brief Summary

The primary endpoint of this study is to estimate morphologic complete remission rate. Estimation of response rate is also a secondary objection.

Detailed Description

Myelodysplastic syndrome (MDS) is a hematological disorder characterized by ineffective hematopoiesis. The only known curative treatment for patients with MDS is allogeneic stem cell transplantation. However, only a minority of patients are candidates for this aggressive therapy. DNA hypomethylation agents have been shown to have activity in this disorder and are postulated to work by reversing this epigenetic mechanism of gene-silencing. Recently, 5-azacitidine, administered subcutaneously for seven days, received approval by the FDA for the therapy of MDS based on a randomized trial which demonstrated a diminished risk of leukemic transformation and improved survival when compared to best supportive care.

The subcutaneous route of administration can present challenges to implementing this therapy. In the CALGB studies 8921 and 9221, approximately 23% of patients had significant injection site pain. Moreover, 35 % of patients had injection site bruising which can be extensive in thrombocytopenic patients. Due to limitations on drug concentration and administration volumes for subcutaneous dosing, patients often need to have two or three injections at separate sites each day to meet target dosing. In addition, the schedule of administration is inconvenient in an outpatient setting secondary to the need to schedule administrations over weekends. Therefore, there is great interest in pursuing an abbreviated intravenous route for administration of the drug.

Conditions

Myelodysplastic Syndromes

Keywords

MDS either de novo or secondary, fitting any of the WHO classifications.

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Azacitidine

Azacitidine 75 mg/m2 IV on days 1-5 of each 28 day cycle. Patients that do not respond after two cycles will have the dose increased to 100 mg/m2. Patients who achieve a CR will receive 3 additional 28 day cycles and then begin treatment on days 1-5 of a 56 day cycle. Individuals who demonstrate a loss of response will resume 28 day cycles.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

Interventions

Azacitidine

Intervention Type: DRUG

Other Intervention Names

5-azacitidine; Vidaza

Eligibility Criteria

Inclusion Criteria

1. Pathological MDS either de novo or secondary, fitting any of the FAB classifications, confirmed by institutional pathologist within 2 weeks prior to start of treatment. Patients with 5% bone marrow blasts must also meet one of the following criteria:

• Symptomatic anemia with either hemoglobin less than 10.0 g/dL or requiring RBC transfusion
• Thrombocytopenia with a history of two or more platelet counts < 50,000 / µL or a significant hemorrhage requiring platelet transfusions, or
• Neutropenia with two or more absolute neutrophil counts less than 1,000 /µL.

2. ECOG performance status of 0-2.

3. Must give written informed consent indicating their awareness of the investigational nature of this study and its potential hazards.

4. Adequate renal and hepatic function (creatinine ≤ 150% of institutional upper limit of normal, total bilirubin ≤ 150% institutional upper limit of normal, AST ≤ 200% institutional upper limit of normal).

5. Life expectancy of at least 12 weeks.

6. Have not received any chemotherapy within 4 weeks of study enrollment and must have recovered from any treatment-related toxicities.

7. Women of childbearing age must have a negative serum pregnancy test prior to initiating therapy.

8. Sexually active women of childbearing potential must use effective birth control during the trial and for an appropriate period after the trial.

9. Men must be willing to avoid fathering a new child while receiving therapy with azacitidine.

10. ≥18 years, no upper age limit

11. Individuals who are candidates for hematopoietic stem cell transplantation and who meet all other study criteria may participate in the study and receive intravenous azacitidine alone as a treatment prior to transplantation.

Exclusion Criteria

1. Known CNS leukemia.

2. Previously received Azacitidine (Vidaza®, Pharmion Corp., Boulder CO) or decitabine (Dacogen®, MGI Pharma Inc. Bloomington, MN).

3. Known or suspected hypersensitivity to azacitidine or mannitol.

4. Receiving any other investigational agents within 30 days of first dose of study drug.

5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.

6. Known positive serology for HIV.

7. Had radiotherapy within 14 days prior to study enrollment.

8. Known presence of hepatic tumors.

9. <18 years of age

10. Exclude women who are pregnant or breast feeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi Vij, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

06-0585

Identifier Type: -

Identifier Source: org_study_id