Acute Myeloid Leukemia, Myelodysplastic Syndrome
Conditions
Keywords
maintenance treatment, stem cell transplant, cytarabine-based chemotherapy
Brief summary
To determine the impact of maintenance therapy in patients with MDS/AML in remission.
Detailed description
We propose a phase II study to determine the impact of maintenance therapy with 5-azacytidine and GM-CSF in patients with poor-risk AML or MDS, who are in remission after definitive treatment with either stem cell transplant or cytarabine-based consolidation chemotherapy. In order to precede relapse and to avoid lead time bias, treatment would need to commence within 185 days of definitive therapy. Furthermore, approximately 50% of relapses occur within the first year and up to 80% within two years after SCT, therefore we would limit the duration of maintenance therapy to one year, followed by two years of follow-up.
Interventions
DRUGAzacitidine
Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
BIOLOGICALSargramostim
Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \> 6 months 2. Initial diagnosis of poor -risk AML or MDS (defined in section 3.2), treated with either stem cell transplant or cytarabine-based consolidation chemotherapy, within the past 60-185 days 3. ECOG performance status 0-2 4. No morphologic evidence of leukemia or active MDS as determined by JHH Hematopathologist independent review of a bone marrow aspirate and biopsy done following the completion of therapy and within 14 days prior to enrollment 5. Peripheral blood count recovery: Neutrophil count ≥ 1000 /µL, platelet count ≥ 50x 109 /µL without platelet transfusions, and adequate hematocrit independent of red cell transfusions . 6. No evidence of extramedullary leukemia, such as CNS or soft tissue involvement 7. Adequate end organ function as measured by the following: AST and ALT \< 4 x normal, total serum bilirubin \< 2 x upper limit normal (unless due to hemolysis, Gilbert's syndrome, or ineffective erythropoiesis), creatinine \< 2 x upper limit of normal 8. Ability to give informed consent 9. In agreement to use an effective barrier method of birth control to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile
Exclusion criteria
1. Patients with untreated or uncontrolled infections 2. Patients with untreated or uncontrolled grade 3 or 4 GVHD 3. Pregnancy and lactation 4. Concurrent use of any other investigational agents. 5. Known HIV-positive patients. 6. Known hypersensitivity to 5AC or GM-CSF
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Two-year Relapse Free Survival of Patients | 2 year | To evaluate the two-year relapse-free survival (RFS) of patients with poor-risk Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS), who receive maintenance treatment with 5-Azacytidine (5AC) in combination with sargramostim (GM-CSF) during remission, following definitive therapy with either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Toxicity as Determined by Anemia | 1 year | Percentage of patients with anemia, the most commonly reported hematologic toxicity, after receiving the combination of Azacitidine and sargramostim |
| One-year RFS | 1 year | We will report the number of participants with one year RFS |
| Overall Survival | 2 years | Percentage of participants with overall survival at 2 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Myeloablative BMT Azacitidine and sargramostim after myeloablative stem cell transplant
Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles. | 1 |
| Non-myeloablative BMT Azacitidine and sargramostim after non-myeloablative stem cell transplant
Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles. | 23 |
| Standard Consolidation Azacitidine and sargramostim after standard consolidation
Azacitidine: Azacitidine will be administered days 1-5 of a 28 day cycle. Treatment is planned for a total of 12 cycles.
Sargramostim: Sargramostim will be administered days 1-10 of a 28 day cycle. Treatment is planned for a total of 12 cycles. | 1 |
| Total | 25 |
Baseline characteristics
| Characteristic | Total | Myeloablative BMT | Non-myeloablative BMT | Standard Consolidation |
|---|---|---|---|---|
| Age, Customized <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=73 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Between 18 and 72 years | 25 Participants | 1 Participants | 23 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 1 Participants | 18 Participants | 1 Participants |
| Sex: Female, Male Female | 12 Participants | 0 Participants | 11 Participants | 1 Participants |
| Sex: Female, Male Male | 13 Participants | 1 Participants | 12 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 17 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 17 / 17 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 4 / 17 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Two-year Relapse Free Survival of Patients
To evaluate the two-year relapse-free survival (RFS) of patients with poor-risk Acute Myeloid Leukemia (AML) or Myelodysplasia (MDS), who receive maintenance treatment with 5-Azacytidine (5AC) in combination with sargramostim (GM-CSF) during remission, following definitive therapy with either a stem cell transplant (SCT) or cytarabine-based consolidation chemotherapy.
Time frame: 2 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-myeloablative BMT | Two-year Relapse Free Survival of Patients | 8 Participants |
| Myeloablative BMT | Two-year Relapse Free Survival of Patients | 1 Participants |
| Standard Consolidation | Two-year Relapse Free Survival of Patients | 1 Participants |
Secondary
Hematologic Toxicity as Determined by Anemia
Percentage of patients with anemia, the most commonly reported hematologic toxicity, after receiving the combination of Azacitidine and sargramostim
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-myeloablative BMT | Hematologic Toxicity as Determined by Anemia | 8 Participants |
| Myeloablative BMT | Hematologic Toxicity as Determined by Anemia | 1 Participants |
| Standard Consolidation | Hematologic Toxicity as Determined by Anemia | 0 Participants |
Secondary
One-year RFS
We will report the number of participants with one year RFS
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-myeloablative BMT | One-year RFS | 12 Participants |
| Myeloablative BMT | One-year RFS | 1 Participants |
| Standard Consolidation | One-year RFS | 1 Participants |
Secondary
Overall Survival
Percentage of participants with overall survival at 2 years.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Non-myeloablative BMT | Overall Survival | 6 Participants |
| Myeloablative BMT | Overall Survival | 1 Participants |
| Standard Consolidation | Overall Survival | 1 Participants |