Study of Three Different Schedules of Low-Dose Decitabine in Myelodysplastic Syndrome (MDS)

NCT ID: NCT00067808

Last Updated: 2012-08-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-10-31

Study Completion Date

2009-05-31

Brief Summary

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The goal of this clinical research study is to learn if decitabine (given at 3 different doses) can help to control Myelodysplastic Syndrome (MDS). The safety of these 3 treatments will also be studied.

Detailed Description

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Treatment: Methylation is a change that occurs to Deoxyribonucleic acid (DNA) that has an effect on gene usage in human cells. Abnormal methylation is very common in leukemias. Decitabine is a new drug that blocks DNA methylation.

Before treatment starts, a physical exam, blood tests (between 4-6 tablespoons), and a bone marrow study will be done. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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 able to have children must have a negative blood or urine pregnancy test.

When this study began, participants were randomly assigned (as in the toss of a coin) to one of 3 treatment groups. The assignment to one of the 3 schedules was adjusted according to how well patients respond to treatment. About 17 patients were assigned to each group for the first 50 patients.

Participants in the first group received decitabine intravenously (IV--through a needle in their vein) over one hour, once a day, for 10 days. Treatment was given every 4 to 8 weeks depending on how well their blood counts recovered. Participants in the second group received decitabine as an IV infusion over one hour, once a day, for 5 days. Treatment was given every 4 to 8 weeks. Participants who received decitabine by vein got the same total dose per course. Participants in the third group received decitabine by subcutaneous (SQ) injections (injections given under the skin) twice a day for 5 days. As in the first and second group, treatment was given every 4 to 8 weeks.

After 65 patients were enrolled on this study, it was decided that the 5-day IV schedule was the best of the 3 schedules. The study will now continue with all new patients receiving the 5 -day IV decitabine treatment. If you are now enrolling on the study, you will be placed in this treatment group, instead of being randomly assigned to a treatment group.

Participants who are already on study and who are receiving the 5-day SQ schedule or the 10-day IV schedule, will be given the option to change to the 5-day IV schedule at the start of their next course of study drug treatment, since this is considered the new "standard" schedule on this particular study.

If you choose to take part in this study and begin receiving the study treatment described above, your response to treatment will be checked after completing 8 weeks of therapy. If the response to treatment is good, treatment with decitabine will continue. Decitabine treatment may be continued for up to 24 courses, or as long as it is judged best to control the leukemia.

During this study, you will need to visit your doctor for a physical exam and 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. Periodic bone marrow samples will also be taken to check cells related to the disease before, during, and after completion of this study.

Patients 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.Up to 133 participants will be treated in this study. All will be enrolled at M. D. Anderson.

Conditions

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Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia

Keywords

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Myelodysplastic Syndrome Chronic Myelomonocytic Leukemia MDS Decitabine Dacogen Methylation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Decitabine 10 mg/m^2 IV

10 mg/m\^2 intravenous (IV) over 1 hour daily for 10 days

Group Type ACTIVE_COMPARATOR

Decitabine

Intervention Type DRUG

10 mg/m\^2 by vein over 1 hour daily for 10 days

Decitabine 20 mg/m2 IV

20 mg/m2 IV over 1 hour daily for 5 days

Group Type ACTIVE_COMPARATOR

Decitabine

Intervention Type DRUG

20 mg/m2 by vein (IV) over 1 hour daily x 5 days

Decitabine 20 mg/m2 SQ

20 mg/m2 subcutaneous (SQ) daily for 5 days

Group Type ACTIVE_COMPARATOR

Decitabine

Intervention Type DRUG

20 mg/m2 subcutaneous (SQ) daily x 5 days

Interventions

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Decitabine

10 mg/m\^2 by vein over 1 hour daily for 10 days

Intervention Type DRUG

Decitabine

20 mg/m2 by vein (IV) over 1 hour daily x 5 days

Intervention Type DRUG

Decitabine

20 mg/m2 subcutaneous (SQ) daily x 5 days

Intervention Type DRUG

Other Intervention Names

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Dacogen Dacogen Dacogen

Eligibility Criteria

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Inclusion Criteria

1. MDS and 5% or more marrow blasts, or IPSS risk intermediate 1-2 or high risk; or chronic myelomonocytic leukemia
2. Performance status 0-2 (Eastern Cooperative Oncology Group (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/m2 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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hagop M Kantarjian, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Oki Y, Jelinek J, Shen L, Kantarjian HM, Issa JP. Induction of hypomethylation and molecular response after decitabine therapy in patients with chronic myelomonocytic leukemia. Blood. 2008 Feb 15;111(4):2382-4. doi: 10.1182/blood-2007-07-103960. Epub 2007 Nov 30.

Reference Type DERIVED
PMID: 18055864 (View on PubMed)

Related Links

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http://www.mdanderson.org

M.D. Anderson Cancer Center's website

Other Identifiers

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ID03-0180

Identifier Type: -

Identifier Source: org_study_id