Trial Outcomes & Findings for Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease (NCT NCT00388362)

NCT ID: NCT00388362

Last Updated: 2017-04-21

Results Overview

Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 36 participants
• Primary outcome timeframe: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus
• Results posted on: 2017-04-21

Participant Flow

Participant milestones

Measure	Sirolimus Therapy Administration of Sirolimus and Prednisone
Enrolled STARTED	36
Enrolled COMPLETED	23
Enrolled NOT COMPLETED	13
Remained on Study Median of 514 Days STARTED	23
Remained on Study Median of 514 Days COMPLETED	21
Remained on Study Median of 514 Days NOT COMPLETED	2

Reasons for withdrawal

Measure	Sirolimus Therapy Administration of Sirolimus and Prednisone
Enrolled Ineligible	1
Enrolled Adverse Event	9
Enrolled Death	1
Enrolled Loss insurance	1
Enrolled Withdrawal by Subject	1
Remained on Study Median of 514 Days Death	2

Baseline Characteristics

Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

Baseline characteristics by cohort

Measure	Sirolimus n=36 Participants Administration of Sirolimus and Prednisone
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus

Population: 23 patients that remained on the study for a median of 514 days (96-814 days). Numbers based on resolution/ improvement in clinical manifestations of cGVHD with a median of 90% reduction in prednisone dose and no additional immunosuppressive therapy over a two year treatment period.

Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment

Outcome measures

Measure	Sirolimus Therapy n=23 Participants Administration of Sirolimus and Prednisone
Clinical Activity Complete Remission	4 participants
Clinical Activity Partial Remission	4 participants

SECONDARY outcome

Timeframe: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus

Population: 23 patients that remained on the study for a median of 514 days (96-814 days), 2 died (1- second cancer and 1- progressive cardiac failure)

Administration of Sirolimus and Prednisone

Outcome measures

Measure	Sirolimus Therapy n=23 Participants Administration of Sirolimus and Prednisone
Overall Survival	21 participants

Adverse Events

Sirolimus Therapy

Serious events: 14 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sirolimus Therapy n=35 participants at risk Administration of Sirolimus and Prednisone
General disorders Death	2.9% 1/35 • Number of events 1 • 2 years after enrollment
Infections and infestations CMV resulting in death	8.6% 3/35 • Number of events 3 • 2 years after enrollment
Respiratory, thoracic and mediastinal disorders Pulmonary	5.7% 2/35 • Number of events 2 • 2 years after enrollment
Respiratory, thoracic and mediastinal disorders Sirolimus associated interstitial pneumonitis	2.9% 1/35 • Number of events 1 • 2 years after enrollment
Respiratory, thoracic and mediastinal disorders Sirolimus associated thrombotic microangiopathy and hypertriglyceridemia resulting in pancreatitis	2.9% 1/35 • Number of events 1 • 2 years after enrollment
Blood and lymphatic system disorders Hematological Disease Relapse	5.7% 2/35 • Number of events 2 • 2 years after enrollment
General disorders Emergent Surgery	2.9% 1/35 • Number of events 1 • 2 years after enrollment
Infections and infestations Metapneumovirus pneumonia, recurrent PE resulting in death	2.9% 1/35 • Number of events 1 • 2 years after enrollment
Infections and infestations Recurrent Viral Pneumonia	5.7% 2/35 • Number of events 2 • 2 years after enrollment

Other adverse events

Measure	Sirolimus Therapy n=35 participants at risk Administration of Sirolimus and Prednisone
Infections and infestations Infection	42.9% 15/35 • Number of events 15 • 2 years after enrollment
Musculoskeletal and connective tissue disorders Edema	22.9% 8/35 • Number of events 8 • 2 years after enrollment
Blood and lymphatic system disorders Cholesterol	5.7% 2/35 • Number of events 2 • 2 years after enrollment
Gastrointestinal disorders Diarrhea	8.6% 3/35 • Number of events 3 • 2 years after enrollment
Blood and lymphatic system disorders hypertriglyceridema	28.6% 10/35 • Number of events 10 • 2 years after enrollment

Additional Information

Laura Johnston, MD

Stanford University

Phone: 650-723-0822

Email: janices1@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place