Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndrome, Leukemia, Clofarabine, MDS
Brief summary
The goal of this clinical research study is to compare the effectiveness of 2 different doses of the drug clofarabine that can be given on a weekly schedule for the treatment of Myelodysplastic Syndrome (MDS). The safety of these two doses will also be compared. Primary Objective: Compare the response rates of two dose schedules of clofarabine in MDS. Secondary Objective: Compare response durations, survivals and side effects of the two schedules.
Detailed description
Clofarabine is a new chemotherapy drug that is designed to interfere with the growth and development of cancer cells. If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups (Groups A and B). Participants in Group A will receive a lower dose of clofarabine. Participants in Group B will receive a higher dose of clofarabine. At first, there will be an equal chance of being assigned to either group. However, as experience increases and more information becomes available, the chance of being assigned to the group that has shown the most effectiveness will increase. You and the study doctor will know to which group you are assigned. Participants will receive clofarabine as a 1-hour infusion into a vein once a day for 5 days in a row. This will be repeated every 4 to 8 weeks. Each 4-8 week period is considered 1 cycle of treatment. For participants in both groups, after each cycle of therapy, they will not receive the next cycle of chemotherapy until their blood counts have recovered and any possible side effects have gone away (for around 4 to 8 weeks). You must stay in Houston for the first treatment cycle (about 4 to 8 weeks) and will be required to return to Houston before receiving each additional cycle of chemotherapy (up to 6 days each cycle). Before every treatment cycle, your doctor will perform a physical exam, including measurement of your weight and vital signs (blood pressure, heart rate, temperature, and breathing rate). You will be asked about the level of your daily activities and how you are feeling. You will have blood samples (about 1-2 teaspoons) collected for routine lab tests 1-2 times a week for the first cycle, then every 2-4 weeks while on therapy. Repeat bone marrow samples will be collected every 1-3 cycles. However, if you complete the study before the third cycle, the bone marrow may be taken then. You may choose to have check-up visits and blood tests with your local doctor. If you show a response and do not experience any severe side effects, you can receive up to a total of 12 cycles of therapy. During each cycle, clofarabine will be given the same way as during the first cycle. However, the dose of clofarabine may be lowered during later cycles to decrease the risk of side effects that may have occurred in previous cycles. If the disease gets worse or you experience any intolerable side effects, you will be taken off the study and your doctor will discuss other treatment options with you. This is an investigational study. Clofarabine is approved by the FDA for treatment of pediatric acute lymphoblastic leukemia. Its use in this study is experimental. Up to 60 participants will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGClofarabine
Group A: 15 mg/m\^2 IV over 1 hour daily for 5 days Group B: 30 mg/m\^2 IV over 1 hour daily for 5 days
Sponsors
Genzyme, a Sanofi Company
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. Patients with MDS and \>/= 5% blasts or International Prognostic Scoring System (IPSS) risk intermediate or high; patients with Chronic Myelomonocytic Leukemia (CMML). 2. No prior intensive chemotherapy or high-dose ara-C (\> 1g/m2). 3. Prior biologic therapies, targeted therapies, or single agent chemotherapy allowed. 4. 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. 5. Hydroxyurea is permitted for control of counts prior to treatment. 6. Procrit, GCSF are allowed before therapy. 7. Performance 0-2 (Eastern Cooperative Oncology Group (ECOG)). Adequate organ function including the following: Adequate liver function (bilirubin of \< 2mg/dl), and renal function (creatinine \< 2mg/dl), and SGPT (ALT) \< 3 \* upper limit of normal (ULN). Adequate cardiac functions (New York Heart Association (NYHA) cardiac III-IV excluded). 8. Signed informed consent.
Exclusion criteria
1. Nursing and pregnant females. 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. 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. 4. Prior clofarabine treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response for Two Dose Schedules of Clofarabine | 4 weeks (minimum 1 cycle) up to 24 weeks (maximum 3 cycles of 8 weeks) | Response defined as Complete Remission (CR): Normalization of blood counts with neutrophils \>/= 1 \* 10\^9/L and platelet counts \>/= 100 \* 10\^9/L, and marrow blasts \</=5%; Partial Remission: as above except for presence of 6-15% marrow blasts, or 50% reduction if \<15% at start of treatment; or Hematologic Improvement (HI): Complete Response (CR) with the exception of a lack of platelet recovery to \>/= 100 \* 10\^9/L. Repeat bone marrow samples collected every 1-3 cycles (4-8 week cycle). |
Countries
United States
Participant flow
Recruitment details
Recruitment Period 1/31/06 - 9/21/09. All patients were registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment details
Of the 60 participants registered on this study, two (2) were excluded prior to receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| 15 mg/m^2 Clofarabine Lower Dose Clofarabine Group A: 15 mg/m\^2 intravenous (IV) over 1 hour daily for 5 days | 37 |
| 30 mg/m^2 Clofarabine Higher Dose Clofarabine Group B: 30 mg/m\^2 IV over 1 hour daily for 5 days | 21 |
| Total | 58 |
Baseline characteristics
| Characteristic | 15 mg/m^2 Clofarabine | 30 mg/m^2 Clofarabine | Total |
|---|---|---|---|
| Age Continuous | 68 Years | 65 Years | 68 Years |
| Region of Enrollment United States | 37 participants | 21 participants | 58 participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 24 Participants | 14 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 37 | 20 / 21 |
| serious Total, serious adverse events | 7 / 37 | 8 / 21 |
Outcome results
Primary
Number of Participants With Response for Two Dose Schedules of Clofarabine
Response defined as Complete Remission (CR): Normalization of blood counts with neutrophils \>/= 1 \* 10\^9/L and platelet counts \>/= 100 \* 10\^9/L, and marrow blasts \</=5%; Partial Remission: as above except for presence of 6-15% marrow blasts, or 50% reduction if \<15% at start of treatment; or Hematologic Improvement (HI): Complete Response (CR) with the exception of a lack of platelet recovery to \>/= 100 \* 10\^9/L. Repeat bone marrow samples collected every 1-3 cycles (4-8 week cycle).
Time frame: 4 weeks (minimum 1 cycle) up to 24 weeks (maximum 3 cycles of 8 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 15 mg/m^2 Clofarabine | Number of Participants With Response for Two Dose Schedules of Clofarabine | Complete Response | 10 Participants |
| 15 mg/m^2 Clofarabine | Number of Participants With Response for Two Dose Schedules of Clofarabine | Hematologic Improvement | 5 Participants |
| 30 mg/m^2 Clofarabine | Number of Participants With Response for Two Dose Schedules of Clofarabine | Complete Response | 5 Participants |
| 30 mg/m^2 Clofarabine | Number of Participants With Response for Two Dose Schedules of Clofarabine | Hematologic Improvement | 1 Participants |