Myelodysplastic Syndrome
Conditions
Keywords
Myelodysplastic Syndrome, 5-azacytidine, allogeneic stem cell transplantation
Brief summary
The purpose of this study is to examine the feasibility and efficacy of using the demethylating agent 5-Azacytidine prior to allogeneic stem cell transplantation in patients with high risk myelodysplastic syndrome (MDS).
Detailed description
The study drug, 5-azacytidine, is given daily intravenously for 7 days. After every 2 cycles study participants will have a bone marrow test to evaluate the effect of the 5-azacytidine on the Myelodysplastic Syndrome (MDS). Participants continue to get cycles of 5-Azacytidine until 2 bone marrow tests show the MDS has stopped responding to the treatment. At that time they will undergo a transplant if a donor is available.
Interventions
DRUG5-azacytidine
The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days.
Sponsors
Celgene Corporation
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients fulfilling the following criteria will be eligible for study entry: 1. Diagnosis of MDS according to WHO criteria 2. Intermediate-2 or high risk by IPSS score 3. Clinically able to receive 5-Azacytidine 4. Serum bilirubin levels \</=1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis 5. Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) levels \</=2 x ULN 6. Serum creatinine levels \</=1.5 x ULN 7. Negative serum pregnancy test prior to 5-Azacytidine treatment for women of childbearing potential 8. Women and men of childbearing potential agree to use contraception while receiving treatment with 5-Azacytidine 9. Potentially eligible for allogeneic transplantation 10. No prior allogeneic transplant 11. Age 18 to 70, inclusive.
Exclusion criteria
1. Known or suspected hypersensitivity to 5-azacytidine or mannitol 2. Patients previously treated with 5-azacytidine or deoxyazacytidine 3. Pregnant or breast feeding 4. Patients with advanced malignant hepatic tumors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation | 1 year | Percentage of patients alive one year after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated one year survival rate from this curve is 50%, while the estimated two year survival rate is 50%. |
| Two Year Overall Survival of Allogeneic Transplant Recipients After Transplantation | 2 years | Percentage of patients alive two years after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated two year survival rate is 50%, the same as one year survival rate. |
| One Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation | 1 year | Percentage of participants that received allogeneic transplant and had event free survival, as estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated one-year event-free survival rate is the same as overall survival, 50%. |
| Two Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation | 2 years | Percentage of participants that received allogeneic transplant and had event free survival. The percentage of patients was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated two-year event-free survival rate is the same as overall survival, 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 1 year | Percentage of participants alive one year after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored. The estimated one year overall survival rate from this curve is 47%. The one year overall survival is the same as one year event free survival rate. |
| Two-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts. | 2 years | Percentage of participants alive two years after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two year survival rate is 37% .The estimated two-year overall survival rate is the same as two-year event free survival. |
| One-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 1 year | Percentage of participants with one year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated one-year event-free survival rate is the same as for overall survival, 47% (SE = 13.6%). |
| Two-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 2 years | Percentage of participants with two year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two- year event-free survival rate is the same as for overall survival, 37% (SE = 14.3%). |
Countries
United States
Participant flow
Recruitment details
This study plans to accrue over one year with a planned 2 year subsequent follow-up. Virginia Commonwealth Unvierstiy (VCU) will be the sole site for this project.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 5-azacytidine 5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.
5-azacytidine: The recommended starting dose for the first treatment cycle, for all patients regardless of baseline hematology laboratory values, is 75 mg/m2 subcutaneously or intravenously, daily for 7 days. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Chose another center for transplant | 1 |
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | Arm A: 5-azacytidine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 9.9 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 13 / 16 |
Outcome results
Primary
One Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation
Percentage of participants that received allogeneic transplant and had event free survival, as estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated one-year event-free survival rate is the same as overall survival, 50%.
Time frame: 1 year
Population: Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | One Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation | 50 percentage of participants |
Primary
One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation
Percentage of patients alive one year after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated one year survival rate from this curve is 50%, while the estimated two year survival rate is 50%.
Time frame: 1 year
Population: Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation | 50 percentage of participants |
Primary
Two Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation
Percentage of participants that received allogeneic transplant and had event free survival. The percentage of patients was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. The estimated two-year event-free survival rate is the same as overall survival, 50%.
Time frame: 2 years
Population: Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | Two Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation | 50 percentage of participants |
Primary
Two Year Overall Survival of Allogeneic Transplant Recipients After Transplantation
Percentage of patients alive two years after their transplantation, as estimated by the Kaplan-Meier survival curve. The estimated two year survival rate is 50%, the same as one year survival rate.
Time frame: 2 years
Population: Patients surviving after stem cell infusion will be considered in the transplantation cohort; those dying or relapsing prior to this event are considered to have progressed. Outcomes of 5-Axacytidine responders and non-responders will be compared. Patients alive at the time of last observation will be censored.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | Two Year Overall Survival of Allogeneic Transplant Recipients After Transplantation | 50 percentage of participants |
Secondary
One-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Percentage of participants with one year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated one-year event-free survival rate is the same as for overall survival, 47% (SE = 13.6%).
Time frame: 1 year
Population: Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | One-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 47 percentage of participants |
Secondary
One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Percentage of participants alive one year after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored. The estimated one year overall survival rate from this curve is 47%. The one year overall survival is the same as one year event free survival rate.
Time frame: 1 year
Population: Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 47 percentage of participants |
Secondary
Two-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts
Percentage of participants with two year event free survival after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two- year event-free survival rate is the same as for overall survival, 37% (SE = 14.3%).
Time frame: 2 years
Population: Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | Two-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts | 37 percentage of participants |
Secondary
Two-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts.
Percentage of participants alive two years after their first treatment was estimated by the Kaplan-Meier survival curve. The events analyzed are evidence of molecular, cytogenetic or histologic relapse or death from any cause. Patients alive at the time of last observation will be censored.The estimated two year survival rate is 37% .The estimated two-year overall survival rate is the same as two-year event free survival.
Time frame: 2 years
Population: Intent to treat analysis including patients who consented and were eligible. Patients enrolled in the study having received at least one 28 day cycle of 5-Azacytidine. As well as engraftment of white blood cells and platelets, graft failure, relapse and Graft Versus Host Disease (GVHD) will be considered in the intent-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A: 5-azacytidine | Two-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts. | 37 percentage of participants |