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

• ClinicalTrials.gov Identifier: NCT00067808
• Recruitment Status: Completed
• First Posted: August 28, 2003
• Results First Posted: May 26, 2011
• Last Update Posted: August 7, 2012
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: Eisai Inc.
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia	Drug: Decitabine	Phase 2

Detailed Description:

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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Study of Three Different Schedules of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS)
• Study Start Date: October 2003
• Actual Primary Completion Date: May 2009
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Decitabine 10 mg/m^2 IV; 10 mg/m^2 intravenous (IV) over 1 hour daily for 10 days	Drug: Decitabine; 10 mg/m^2 by vein over 1 hour daily for 10 days; Other Name: Dacogen
Active Comparator: Decitabine 20 mg/m2 IV; 20 mg/m2 IV over 1 hour daily for 5 days	Drug: Decitabine; 20 mg/m2 by vein (IV) over 1 hour daily x 5 days; Other Name: Dacogen
Active Comparator: Decitabine 20 mg/m2 SQ; 20 mg/m2 subcutaneous (SQ) daily for 5 days	Drug: Decitabine; 20 mg/m2 subcutaneous (SQ) daily x 5 days; Other Name: Dacogen

Outcome Measures

Primary Outcome Measures :

1. Participant Responses [ Time Frame: Response to treatment after 8 weeks of therapy ]
   Objective responses by International Working Group criteria: 'Complete Response' (CR) defined as Normalization of the peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 109/ L, and a platelet count > 100 x 109/L); 'Other Response' including Partial Remission (PR) defined as above, except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment combined with participants who meet all criteria for CR except for platelet recovery to >100 x 109/L; and 'No Response'.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Texas

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Eisai Inc.

Investigators

• Principal Investigator: Hagop M Kantarjian, MD; M.D. Anderson Cancer Center

More Information

Additional Information:

M.D. Anderson Cancer Center's website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2007 Nov 30.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00067808
• Other Study ID Numbers: ID03-0180
• First Posted: August 28, 2003
• Results First Posted: May 26, 2011
• Last Update Posted: August 7, 2012
• Last Verified: August 2012

Keywords provided by M.D. Anderson Cancer Center:

Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; MDS; Decitabine; Dacogen; Methylation

Additional relevant MeSH terms:

Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome; Disease; Pathologic Processes; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Decitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors