5-Azacytidine Prior to Allogeneic Stem Cell Transplant in High Risk Myelodysplastic Syndrome

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Study of the Use of 5-Azacytidine as Pre-Transplant Cytoreduction Prior to Allogeneic Stem Cell Transplantation for High Risk Myelodysplastic Syndromes

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: 5-azacytidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfilling the following criteria will be eligible for study entry: Diagnosis of MDS according to WHO criteria Intermediate-2 or high risk by IPSS score Clinically able to receive 5-Azacytidine 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 Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) levels </=2 x ULN Serum creatinine levels </=1.5 x ULN Negative serum pregnancy test prior to 5-Azacytidine treatment for women of childbearing potential Women and men of childbearing potential agree to use contraception while receiving treatment with 5-Azacytidine Potentially eligible for allogeneic transplantation No prior allogeneic transplant Age 18 to 70, inclusive. Exclusion Criteria: Known or suspected hypersensitivity to 5-azacytidine or mannitol Patients previously treated with 5-azacytidine or deoxyazacytidine Pregnant or breast feeding Patients with advanced malignant hepatic tumors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: 5-azacytidine<br>5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes. | Drug: 5-azacytidine<br>* 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.<br>* Other names: U-18496;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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%. | 1 year | 
| 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. | 2 years | 
| 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%. | 1 year | 
| 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%. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year | 
| 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. | 2 years | 
| 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%). | 1 year | 
| 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%). | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndrome, 5-azacytidine, allogeneic stem cell transplantation