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

Myelodysplastic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721214
• Other study ID #: MCC-11328
• Status: Completed
• Phase: Phase 2
• First received: July 22, 2008
• Last updated: February 3, 2016
• Start date: July 2008
• Est. completion date: June 2014

Study information

• Verified date: February 2016
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
United States	Massey Cancer Center / Virginia Commonwealth University	Richmond	Virginia

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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%.	1 year	No
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.	2 years	No
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%.	1 year	No
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%.	2 years	No
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.	1 year	No
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.	2 years	No
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%).	1 year	No
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%).	2 years	No