Phase II Study of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS) Post Azacytidine (AZA) Failure


Phase 2
N/A
N/A
Not Enrolling
Both
Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia

Thank you

Trial Information

Phase II Study of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS) Post Azacytidine (AZA) Failure


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is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large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.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Overall Response

Outcome Description:

Participants with Overall Response, categorized as 'Complete Response' to represent remission or 'No Complete Response' for lack of remission. Response evaluation after completing one course of therapy (8-12 weeks), then bone marrow aspiration to document remission every 1-3 courses.

Outcome Time Frame:

Blood tests baseline and after completing 8-12 weeks of therapy

Safety Issue:

No

Principal Investigator

Hagop Kantarjian, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

2004-0468

NCT ID:

NCT00113321

Start Date:

March 2005

Completion Date:

November 2008

Related Keywords:

  • Myelodysplastic Syndrome
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome
  • Chronic Myelomonocytic Leukemia
  • Azacytidine Failure
  • Decitabine
  • Leukemia
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute

Name

Location
UT MD Anderson Cancer Center Houston, Texas  77030