Trial Outcomes & Findings for 5-Azacytidine Prior to Allogeneic Stem Cell Transplant in High Risk Myelodysplastic Syndrome (NCT NCT00721214)

Last Updated: 2016-03-02

Results Overview

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%.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

1 year

Results posted on

2016-03-02

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	16
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Chose another center for transplant	1
Overall Study Death	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: 5-azacytidine n=16 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	54 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=12 Participants 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.
One Year Overall Survival of Allogeneic Transplant Recipients After Transplantation	50 percentage of participants Interval 20.0 to 80.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=12 Participants 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.
Two Year Overall Survival of Allogeneic Transplant Recipients After Transplantation	50 percentage of participants Interval 20.0 to 80.0

PRIMARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=12 Participants 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.
One Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation	50 percentage of participants Interval 20.0 to 80.0

PRIMARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=12 Participants 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.
Two Year Event Free Survival (EFS) for Allogeneic Transplant Recipients After Transplantation	50 percentage of participants Interval 20.0 to 80.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=16 Participants 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.
One-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts	47 percentage of participants Interval 20.0 to 74.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=16 Participants 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.
Two-year Overall Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts.	37 percentage of participants Interval 9.0 to 65.0

SECONDARY outcome

Timeframe: 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%).

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=16 Participants 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.
One-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts	47 percentage of participants Interval 20.0 to 74.0

SECONDARY outcome

Timeframe: 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%).

Outcome measures

Outcome measures
Measure	Arm A: 5-azacytidine n=16 Participants 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.
Two-year Event-free Survival From Time of Treatment Initiation With 5-Azacytidine for All Study Cohorts	37 percentage of participants Interval 9.0 to 65.0

Adverse Events

Arm A: 5-azacytidine

Serious events: 13 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A: 5-azacytidine n=16 participants at risk 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.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify, death-died of progressive MDS)	25.0% 4/16 • Number of events 4 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Blood and lymphatic system disorders Blood/Bone Marrow- Other	25.0% 4/16 • Number of events 4 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Nervous system disorders Seizure	6.2% 1/16 • Number of events 2 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Hepatobiliary disorders Cholecystitis	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Gastrointestinal disorders Pain - Abdomen NOS	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Gastrointestinal disorders Nausea	6.2% 1/16 • Number of events 2 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Investigations Fatigue	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Blood and lymphatic system disorders Infection	12.5% 2/16 • Number of events 2 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Respiratory, thoracic and mediastinal disorders Hemorrhage	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Blood and lymphatic system disorders Opportunistic infection associated with >=Grade 2 Lymphopenia	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Infections and infestations Died of Sepsis	18.8% 3/16 • Number of events 3 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Gastrointestinal disorders Perforation	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Infections and infestations Febrile Neutropenia	6.2% 1/16 • Number of events 1 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.
Skin and subcutaneous tissue disorders Myositis	6.2% 1/16 • Number of events 4 • 3 years Reportable adverse events include relapse, graft failure, any other unexpected grade 3 or 4 that in the opinion of investigator may be related to protocol treatment or death from any cause. All hospitalizations and serious infections (requiring IV antibiotics) will be reported on regular follow-up forms. All other AEs not reportable per protocol.

Other adverse events

Adverse event data not reported

Additional Information

John M. McCarty, MD

Massey Cancer Center

Phone: 804-828-4360

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place