Trial Outcomes & Findings for Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant (NCT NCT00660400)

Last Updated: 2014-09-22

Results Overview

Relapse-free survival one year after allogeneic HCT in MDS patients receiving at least one complete cycle of 5-azacitidine (Vidaza) in the pre-transplantation setting. Relapsed disease: if with complete remission (CR) - greater than 5% blasts in bone marrow; if with partial response (PR) - greater than 30% increase in blasts in the marrow; if with stable disease (SD) - return to pretreatment peripheral blood levels and transfusion requirements due to disease.

Recruitment status

COMPLETED

Study phase

Target enrollment

25 participants

Primary outcome timeframe

One year post allogeneic HCT

Results posted on

2014-09-22

Participant Flow

From 05/2008 to 08/2010, 25 patients with Myelodysplastic Syndrome (MDS) were enrolled to the study at Moffitt Cancer Center.

Four patients did not proceed to allogeneic HCT.

Participant milestones

Participant milestones
Measure	Combined Therapy 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Overall Study STARTED	25
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Combined Therapy 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Overall Study Lack of insurance approval	1
Overall Study Suboptimal organ function	1
Overall Study Intracranial hemorrhage	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Pre-Transplant 5-Azacitidine In Patients With High-Risk Myelodysplastic Syndrome Who Are Candidates For Allogeneic Hematopoietic Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Combined Therapy n=25 Participants 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Age, Continuous	55 years n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: One year post allogeneic HCT

Population: Participants who proceeded to allogeneic HCT

Outcome measures

Outcome measures
Measure	Combined Therapy n=21 Participants 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Percentage of Participants With Relapse-free Survival (RFS)	52 percentage of participants Interval 30.0 to 71.0

SECONDARY outcome

Timeframe: At the end of up to six (28 day) cycles of 5-azacitidine

Population: Participants who proceeded to allogeneic HCT

Pre-allogeneic HCT responses to 5-azacitidine (Vidaza), based on the International Working Group criteria: Complete Remission (CR); Partial Response (PR); Stable Disease (SD). Point estimates and 95% confidence intervals were calculated for the response rate to 5-azacitidine, evaluated at marrow evaluation after 4 cycles of 5-azacitidine or prior to HCT whichever came first. CR: Bone marrow with 5% myeloblasts and normal maturation of all cell lines. PR: All CR criteria if abnormal before treatment except bone marrow blasts decreased by 50% over pretreatment but still \> 5%. SD: Failure to attain CR, PR, relapsed (or progressive) disease.

Outcome measures

Outcome measures
Measure	Combined Therapy n=21 Participants 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Overall Response Rate (ORR) Partial Response	48 percentage of participants
Overall Response Rate (ORR) Complete Remission	0 percentage of participants
Overall Response Rate (ORR) Stable Disease	33 percentage of participants
Overall Response Rate (ORR) Progressive Disease	19 percentage of participants

SECONDARY outcome

Timeframe: Up to 3 years

Population: All participants

Proportion of patients enrolled who subsequently proceeded to allogeneic HCT.

Outcome measures

Outcome measures
Measure	Combined Therapy n=25 Participants 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Percentage of Participants Who Proceed to Hematopoietic Cell Transplantation (HCT)	84 percentage of participants

SECONDARY outcome

Timeframe: One year

Population: Participants who proceeded to allogeneic HCT

Overall survival for all participants at one year after first dose of 5-azacitidine (Vidaza). Overall survival was calculated by the method of Kaplan-Meier with standard errors computed using Greenwood's formula.

Outcome measures

Outcome measures
Measure	Combined Therapy n=21 Participants 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Percentage of Participants With Overall Survival (OS)	62 percentage of participants Interval 38.0 to 79.0

Adverse Events

Combined Therapy

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Combined Therapy n=25 participants at risk 5-azacitidine therapy followed Allogeneic Hematopoietic Cell Transplantation (HCT).
Renal and urinary disorders Renal failure	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Infections and infestations Infection - Other, sepsis	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Vascular disorders Deep venous thrombosis	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Nervous system disorders Cerebrovascular accident	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
General disorders Constitutional symptoms - Other, fatigue	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
General disorders Constitutional symptoms - Other, anorexia	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Number of events 3 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Infections and infestations Febrile neutropenia	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Infections and infestations Infection (documented clinically or microbiologically) - skin (cellulitis)	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Infections and infestations Infection with unknown ANC - Lung (pneumonia)	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Metabolism and nutrition disorders Creatinine - Acute renal failure	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Nervous system disorders Neurology - Other, weakness	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Nervous system disorders Neurology - Other - numbness, tingling	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other, pneumonia	4.0% 1/25 • Number of events 1 • 3 years, 4 months This was a standard of care study for Myelodysplastic Syndrome patients, with 5-Azacitidine prior to standard transplant.

Other adverse events

Adverse event data not reported

Additional Information

Teresa Field, M.D., Ph.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-7202

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place