Leukemia
Conditions
Keywords
Leukemia, Myelodysplastic Syndrome, MDS, Azacytidine, 5-Azacytidine, 5-AZA, Vidaza, 5-AZC, Aza-CR, Ladakamycin, NSC-102816, GM-CSF, Sargramostim, Leukine
Brief summary
The goal of this clinical research study is to learn if the combination of azacitidine and GM-CSF can help to control MDS. The safety of these drugs will also be studied. Azacitidine is designed to block certain proteins that stop the function of tumor-fighting genes. By blocking the bad proteins, the tumor-fighting genes may be able to work better. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is designed to help produce white blood cells. This may help to fight infections.
Detailed description
Study Drug Administration: If you are found to be eligible to take part in this study, on Days 1-4 of every cycle, you will receive azacitidine by vein over 15-30 minutes. You may receive drugs to help prevent nausea and vomiting before you receive your dose of azacitidine. On Days 5-7 of every cycle, you will receive GM-CSF by vein over about 15 minutes or by injection. Each study cycle will be about 4-6 weeks, depending on the study doctor's decision. Study Visits: One (1) time each week during every cycle, blood (about 2-3 teaspoons) will be drawn for routine tests. At any time, if your doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease. Length of Study: You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your follow-up visits will be per standard of care for the disease. This is an investigational study. Both azacitidine and GM-CSF are FDA approved and commercially available for the treatment of MDS. The study drug combination to treat MDS is considered investigational. Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGAzacytidine
Starting dose: 40 mg/m\^2 intravenously (IV) or subcutaneously (SQ) daily for 4 days.
DRUGGM-CSF
250 mcg/m\^2 IV or SQ one day (the next day) after completion of azacytidine treatment, for 3 consecutive days.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with low- or intermediate-1-risk MDS according to the International Prognostic Scoring System (IPSS) classification 2. Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UT MD Anderson Cancer Center. 3. Age \>/= 18 years old. 4. Prior therapy with growth factor support, lenalidomide, or other investigational agents is allowed. 5. Previously untreated patients are eligible for this study.
Exclusion criteria
1. Any previous adverse reaction (\>/= Common Terminology Criteria for Adverse Events (CTCAE) grade 2) to GM-CSF. 2. Prior treatment with azacytidine or decitabine. 3. Unresolved diarrhea \>/= CTCAE grade 2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Baseline up to 2 treatment cycles (8 weeks) | ORR is percentage total participants with overall response (Complete Response (CR) or Partial Response (PR)) within two treatment cycles. Response based on modified International Working Group (IWG) criteria: Complete response - Bone marrow: 5% myeloblasts with normal maturation of all cell lines, Persistent dysplasia noted, Peripheral blood Hgb 11 g/dL, Platelets 100x109/L, Neutrophils 1.0x109/L, Blasts 0%. Partial response: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by 50% over pretreatment but still \> 5% , Cellularity and morphology not relevant; Stable disease - Failure to achieve at least PR, but no evidence of progression for \> 8 weeks; No Response or Failure - Death during treatment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS French-American-British (FAB) classification subtype than pretreatme |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 3/15/2012 through 1/14/2013. All participants recruited at The University of Texas MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Azacytidine + GM-CSF Azacytidine administered intravenously (IV) or subcutaneously (SQ) at starting dose of 40 mg/m\^2, daily for 4 days.
GM-CSF administered IV or subcutaneously at 250 mcg/m\^2 one day (the next day) after completion of azacytidine treatment, for 3 consecutive days.
Each treatment cycle lasts at least 4 weeks. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Azacytidine + GM-CSF |
|---|---|
| Age, Continuous | 69 Years |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 3 / 8 |
Outcome results
Primary
Overall Response Rate (ORR)
ORR is percentage total participants with overall response (Complete Response (CR) or Partial Response (PR)) within two treatment cycles. Response based on modified International Working Group (IWG) criteria: Complete response - Bone marrow: 5% myeloblasts with normal maturation of all cell lines, Persistent dysplasia noted, Peripheral blood Hgb 11 g/dL, Platelets 100x109/L, Neutrophils 1.0x109/L, Blasts 0%. Partial response: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by 50% over pretreatment but still \> 5% , Cellularity and morphology not relevant; Stable disease - Failure to achieve at least PR, but no evidence of progression for \> 8 weeks; No Response or Failure - Death during treatment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS French-American-British (FAB) classification subtype than pretreatme
Time frame: Baseline up to 2 treatment cycles (8 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Azacytidine + GM-CSF | Overall Response Rate (ORR) | Complete Response (CR) | 0 percentage of participants |
| Azacytidine + GM-CSF | Overall Response Rate (ORR) | Partial Response (PR) | 0 percentage of participants |
| Azacytidine + GM-CSF | Overall Response Rate (ORR) | No Response | 100 percentage of participants |