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

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndromes

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Trial Information

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

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.

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

- 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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To estimate the rate of complete remission (CR) and partial remission (PR) after four cycles of therapy in patients with high risk myelodysplastic syndrome (MDS).

Outcome Time Frame:

After cycle 4

Safety Issue:


Principal Investigator

Ravi Vij, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

August 2006

Completion Date:

March 2010

Related Keywords:

  • Myelodysplastic Syndromes
  • MDS either de novo or secondary, fitting any of the WHO classifications.
  • Myelodysplastic Syndromes
  • Preleukemia



Washington University School of Medicine Saint Louis, Missouri  63110