Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, MDS, Decitabine, Dacogen, Methylation
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.
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a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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.
Interventions
DRUGDecitabine
10 mg/m\^2 by vein over 1 hour daily for 10 days
Sponsors
Eisai Inc.
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Responses | 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'. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period 6/4/03 - 5/18/09; all patients were registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment details
Enrollment of 128 patients: 1 patient withdrew consent prior to treatment; 3 did not meet eligibility requirement for a total of 124 evaluable patients.
Participants by arm
| Arm | Count |
|---|---|
| Decitabine 10 mg/m2 IV 10 mg/m2 by vein (IV) over 1 hour daily for 10 days | 17 |
| Decitabine 20 mg/m2 IV 20 mg/m2 IV over 1 hour daily for 5 days | 93 |
| Decitabine 20 mg/m2 SQ 20 mg/m2 subcutaneous (SQ) daily for 5 days | 14 |
| Total | 124 |
Baseline characteristics
| Characteristic | Decitabine 20 mg/m2 IV | Decitabine 20 mg/m2 SQ | Decitabine 10 mg/m2 IV | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 48 Participants | 7 Participants | 10 Participants | 65 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 7 Participants | 7 Participants | 59 Participants |
| Age Continuous | 65 years | 64 years | 67 years | 65 years |
| Region of Enrollment United States | 93 participants | 14 participants | 17 participants | 124 participants |
| Sex: Female, Male Female | 33 Participants | 4 Participants | 3 Participants | 40 Participants |
| Sex: Female, Male Male | 60 Participants | 10 Participants | 14 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 17 | 32 / 93 | 8 / 14 |
| serious Total, serious adverse events | 5 / 17 | 32 / 93 | 7 / 14 |
Outcome results
Primary
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'.
Time frame: Response to treatment after 8 weeks of therapy
Population: As treated: 124 patients completed treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Decitabine 10 mg/m2 IV | Participant Responses | No Response | 7 Participants |
| Decitabine 10 mg/m2 IV | Participant Responses | Other Response | 6 Participants |
| Decitabine 10 mg/m2 IV | Participant Responses | Complete Response | 4 Participants |
| Decitabine 20 mg/m2 IV | Participant Responses | No Response | 25 Participants |
| Decitabine 20 mg/m2 IV | Participant Responses | Complete Response | 47 Participants |
| Decitabine 20 mg/m2 IV | Participant Responses | Other Response | 21 Participants |
| Decitabine 20 mg/m2 SQ | Participant Responses | Other Response | 4 Participants |
| Decitabine 20 mg/m2 SQ | Participant Responses | Complete Response | 4 Participants |
| Decitabine 20 mg/m2 SQ | Participant Responses | No Response | 6 Participants |