Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndrome, MDS, Erythropoietin, Darbepoetin alfa, Aranesp, Erythropoiesis stimulating protein, G-CSF, Filgrastim, Neupogen, Prednisone, Cyclosporin A, Sandimmune, CYA, Cyclosporine
Brief summary
Objectives: Primary: To evaluate the response rate of total cytokine-immunotherapy for low-risk myelodysplastic syndromes (MDS). Secondary: To evaluate response duration, survival and side effects of the treatment.
Detailed description
MDS is a disease that produces low blood counts and may cause anemia, infections, and/or bleeding. Erythropoietin and Granulocyte colony-stimulating factor (G-CSF or GCSF) are drugs that stimulate the production of red cells and white cells. Prednisone and cyclosporin are drugs that work against MDS by affecting your immune system. Before you can start treatment on this study, you will have what are called screening tests. These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. Routine blood tests (between 4-6 tablespoons) will be performed. You will have a bone marrow aspiration. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle.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 who are able to have children must have a negative blood or urine pregnancy test. If you are found to be eligible to take part in this study, you will receive erythropoietin as an injection under the skin once a week and G-CSF as an injection under the skin 1-2 times a week for as long as you respond well to treatment. You will take prednisone by mouth every day for a month and cyclosporin tablets by mouth every day for 6 months. During this study, you will need to visit your doctor for a physical exam and measurement of your vital signs. The frequency of doctor visits will vary depending on your physical condition, but will be required at least once every 3 months. Blood tests (about 2 teaspoons) will be done about every 1-2 weeks during the first 12 weeks of treatment, then every 2 to 4 weeks for the remainder of the study. The blood samples will be collected for routine lab tests. Periodic (every 3 to 6 months) bone marrow samples will also be taken to check cells related to the disease before, during, and after completion of this study. You will be taken off study if the disease gets worse or intolerable side effects occur. This is an investigational study. All drugs are FDA approved and commercially available. Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUGErythropoietin
40,000 units injected under the skin (SQ) weekly
DRUGCyclosporin A
300 mg (tablets) by mouth daily for 6 months
DRUGG-CSF
300 mcg injected under the skin (SQ) two times per week
DRUGPrednisone
60 mg per day for 7 days, taper over 1 month
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patients with MDS and \</= 10% blasts or International Prognostic Scoring System (IPSS) low or intermediate 1. No prior intensive chemotherapy or high-dose ara-C (\>/= 1g/m2). Prior cytokines, biologic therapies, targeted therapies, or single agent chemotherapy allowed. Procrit, G-CSF are allowed before therapy. Patients with blasts \< 5% must have an indication for therapy, such as transfusion needs, symptomatic anemia or Hb \< 11g/dl, platelets \< 100 x 10 9/L, or granulocytes \< 10 9/L. 2. Performance 0-2 (Eastern Cooperative Oncology Group (ECOG)). Adequate liver function (bilirubin of \< 2mg/dl) and renal function (creatinine \< 2mg/dl). Adequate cardiac functions (New York Heart Association (NYHA) cardiac III-IV excluded) 3. Signed informed consent
Exclusion criteria
1. Nursing and pregnant females are excluded. Women 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response | Response evaluation within first 3 months from start of therapy, then every 3 to 6 months | Periodic bone marrow samples (every 3-6 months) to check cells related to disease before/during/after study. Response classifications categorized by the International Working Group Response Criteria for Myelodysplastic Syndrome (MDS) as: Complete Remission, Partial Response, Hematologic Improvement or No Response. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period 6/15/04 - 6/1/09; all patients were registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment details
Of fifteen patients enrolled, fourteen patients registered were evaluable and one patient taken off study never having received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Cytokine-Immunotherapy Erythropoietin 40,000 units subcutaneously (SQ) weekly; G-CSF 300 mcg SQ twice per week; Prednisone 60 mg/Day for 7 days, taper over 1 month; Cyclosporin A 300 mg orally daily | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Cytokine-Immunotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age Continuous | 65 Years |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 14 |
| serious Total, serious adverse events | 11 / 14 |
Outcome results
Primary
Number of Participants With Response
Periodic bone marrow samples (every 3-6 months) to check cells related to disease before/during/after study. Response classifications categorized by the International Working Group Response Criteria for Myelodysplastic Syndrome (MDS) as: Complete Remission, Partial Response, Hematologic Improvement or No Response.
Time frame: Response evaluation within first 3 months from start of therapy, then every 3 to 6 months
Population: All treated patients on study included in analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cytokine-Immunotherapy | Number of Participants With Response | Complete Remission | 2 participants |
| Cytokine-Immunotherapy | Number of Participants With Response | Partial Response | 2 participants |
| Cytokine-Immunotherapy | Number of Participants With Response | Hematologic Improvement | 4 participants |
| Cytokine-Immunotherapy | Number of Participants With Response | No Response | 6 participants |