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

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

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).

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: 5-azacytidine

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Massey Cancer Center / Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: 5-azacytidine; 5-azacytidine as pre-transplant cytoreduction prior to allogeneic stem cell transplantation for High Risk Myelodysplatic Syndromes.	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.; Other Names: 5-AC; 5-AZC; Mylosar; U-18496; Vidaza

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: Celgene Corporation
• Investigators: Study Chair: John M. McCarty, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: July 22, 2008
• First Submitted That Met QC Criteria: July 22, 2008
• First Posted (Estimate): July 24, 2008

Study Record Updates

• Last Update Posted (Estimate): March 2, 2016
• Last Update Submitted That Met QC Criteria: February 3, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndrome; allogeneic stem cell transplantation; 5-azacytidine
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: MCC-11328