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

Phase II Randomized Study of Three Different Schedules of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Decitabine; Drug: Decitabine; Drug: Decitabine

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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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 Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas - MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: Dacogen; Drug: Decitabine; 20 mg/m2 by vein (IV) over 1 hour daily x 5 days; Other Names: Dacogen; Drug: Decitabine; 20 mg/m2 subcutaneous (SQ) daily x 5 days; Other Names: Dacogen
Active Comparator: Decitabine 20 mg/m2 IV; 20 mg/m2 IV over 1 hour daily for 5 days	Drug: Decitabine; 10 mg/m^2 by vein over 1 hour daily for 10 days; Other Names: Dacogen; Drug: Decitabine; 20 mg/m2 by vein (IV) over 1 hour daily x 5 days; Other Names: Dacogen; Drug: Decitabine; 20 mg/m2 subcutaneous (SQ) daily x 5 days; Other Names: Dacogen
Active Comparator: Decitabine 20 mg/m2 SQ; 20 mg/m2 subcutaneous (SQ) daily for 5 days	Drug: Decitabine; 10 mg/m^2 by vein over 1 hour daily for 10 days; Other Names: Dacogen; Drug: Decitabine; 20 mg/m2 by vein (IV) over 1 hour daily x 5 days; Other Names: Dacogen; Drug: Decitabine; 20 mg/m2 subcutaneous (SQ) daily x 5 days; Other Names: Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Responses	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'.	Response to treatment after 8 weeks of therapy

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Eisai Inc.
• Investigators: Principal Investigator: Hagop M Kantarjian, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• M.D. Anderson Cancer Center's website

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: August 27, 2003
• First Submitted That Met QC Criteria: August 27, 2003
• First Posted (Estimate): August 28, 2003

Study Record Updates

• Last Update Posted (Estimate): August 7, 2012
• Last Update Submitted That Met QC Criteria: August 1, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Decitabine; Dacogen; MDS; Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Methylation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia; Leukemia, Myeloid; Syndrome; Myelodysplastic Syndromes; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: ID03-0180