Clinical trial NCT00113321: Low-Dose Decitabine in Myelodysplastic Syndrome Post Azacytidine Failure
Official title: Phase II Study of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS) Post Azacytidine (AZA) Failure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Keywords: Myelodysplastic Syndrome
Chronic Myelomonocytic Leukemia
Azacytidine Failure
Decitabine
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2005-06-08
Enrollment: 16
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To study if decitabine can help to control Myelodysplastic Syndrome (MDS) in patients who have failed on therapy with azacytidine, the current standard of therapy.

Detailed description: Methylation is a change that occurs to Deoxyribonucleic acid (DNA) that affects gene usage in human cells. Abnormal methylation is very common in leukemias, which is a related disease to MDS. Decitabine is a new drug that blocks DNA methylation. Researchers want to find out if blocking methylation will help control MDS.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a physical exam, routine blood tests (between 4-6 tablespoons), and a bone marrow aspirate. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will receive decitabine by vein over one hour, once a day, for 5 days (1 course). If this is not possible due to complications, you will receive the drug as an injection under the skin twice a day for 5 days (1 course). Treatment will be given every 4 to 8 weeks depending on how well your blood counts recover.

After completing 8-12 weeks of therapy, response will be evaluated. If the response to treatment is good, treatment with decitabine will continue. Decitabine treatment may be continued for up to 12 courses, or as long as it is judged best to control the leukemia.

During this study, you will need to visit your doctor periodically for physical exams and measurement of vital signs. The frequency of doctor visits will vary depending on your physical condition, but will be required at least once a month.

Blood tests (about 2 teaspoons) will be done about every week during the first 6-8 weeks of treatment, then every 1 to 2 weeks for the length of the study. The blood samples will be used for routine lab tests. Every 1-3 courses, bone marrow samples will also be taken to check cells related to the disease before, during (every 1-3 courses), and after completion of this study.

You will be taken off study if the disease gets worse or intolerable side effects occur.

This is an investigational study. Decitabine is not yet Food and Drug Administration (FDA)approved. It will be provided free of charge by MGI Pharma. Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility criteria: Inclusion Criteria:

1. MDS and 5% or more marrow blasts, or IPSS risk intermediate 1-2 or high risk; or chronic myelomonocytic leukemia. Patients must have failed therapy with azacytidine.
2. Performance status 0-2 (ECOG scale); adequate hepatic (bilirubin \< 2 mg/dl) and renal functions (creatinine \<2mg/dl); New York Heart Association (NYHA)cardiac status III-IV excluded.
3. Signed informed consent.
4. No prior intensive combination chemotherapy or high-dose ara-C (\>/= 1g/m\*2 per dose). Prior biologic therapies, targeted therapies and single agent chemotherapy allowed.
5. Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy.

Exclusion Criteria:

1. Nursing and pregnant females are excluded. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
2. Patients with active and uncontrolled infections.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

Primary outcomes:
measure: Overall Response
timeFrame: Blood tests baseline and after completing 8-12 weeks of therapy
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Hagop Kantarjian, MD
role: PRINCIPAL_INVESTIGATOR
References: