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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
NCT00721214
First received: July 22, 2008
Last updated: July 6, 2015
Last verified: July 2015
  Purpose

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).


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: 5-azacytidine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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%).


Enrollment: 16
Study Start Date: July 2008
Estimated Study Completion Date: December 2015
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Mylosar
  • Vidaza
  • 5-AC
  • 5-AZC
  • U-18496

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00721214

Locations
United States, Virginia
Massey Cancer Center / Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
Celgene Corporation
Investigators
Study Chair: John M. McCarty, MD Virginia Commonwealth University
  More Information

No publications provided

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT00721214     History of Changes
Other Study ID Numbers: MCC-11328
Study First Received: July 22, 2008
Results First Received: April 29, 2015
Last Updated: July 6, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
Myelodysplastic Syndrome
5-azacytidine
allogeneic stem cell transplantation

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Azacitidine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015