Trial Outcomes & Findings for Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT) (NCT NCT00141739)

Last Updated: 2017-01-30

Results Overview

In order to determine whether etanercept, given prophylactically along with a standard Graft Versus Host Disease (GVHD) prevention regimen, will decrease the 100-day mortality and the rate of acute GVHD after allogeneic hematopoietic stem cell transplantation(HSCT), the incidence of grades 2-4 and grades 3-4 GVHD were calculated. GVHD can be clinically graded as 0, I, II, III, or IV. Definition of grades are: Grade 0 - No stage 1-4 of any organ Grade I - Stage 1-2 rash and no liver or gut involvement Grade II - Stage 3 rash, or Stage 1 liver involvement, or Stage 1 gastrointestinal involvement Grade III - Stage 0-3 skin, with STage 2-3 liver, or Stage 2-3 gastrointestinal involvement Grade IV - Stage 4 skin, liver, or gastrointestinal involvement

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

100 days

Results posted on

2017-01-30

Participant Flow

The study was conducted with recruitment taking place at the Blood and Marrow Transplantation Programs of the University of Michigan in Ann Arbor, Michigan and at Loyola University Medical Center, in Maywood, Illinois. The patients participating in this study, underwent transplantation, dating from April 2005-November 2009.

Patients \>1 year of age who were candidates for a myeloablative allo-hemopoietic cell transplant were eligible for inclusion. Donors and recipients were required to match for 7/8 or 8/8 HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci. Patients with an 8/8 HLA-matched related donor were not eligible.

Participant milestones

Participant milestones
Measure	GVHD Prophylaxis GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Overall Study STARTED	100
Overall Study COMPLETED	100
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GVHD Prophylaxis n=100 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Age, Continuous	47 years FULL_RANGE 5 • n=5 Participants
Gender Female	43 Participants n=5 Participants
Gender Male	57 Participants n=5 Participants
Region of Enrollment United States	100 participants n=5 Participants
Disease status at transplantation Low risk	39 participants n=5 Participants
Disease status at transplantation Intermediate risk	33 participants n=5 Participants
Disease status at transplantation High risk	28 participants n=5 Participants
Donor match 8/8 matched unrelated	71 participants n=5 Participants
Donor match 7/8 mismatched unrelated	26 participants n=5 Participants
Donor match 7/8 mismatched related	3 participants n=5 Participants
Conditioning Regimen Parameter Non-Total body radiation	71 participants n=5 Participants
Conditioning Regimen Parameter Total body radiation	29 participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days

Population: To provide Sufficient power

Outcome measures

Outcome measures
Measure	GVHD Prophylaxis n=100 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.	Non-TBI GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Incidence of Grades 2-4 GVHD	45 percentage of participants Interval 95.0 to 105.0	—
The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Incidence of Grades 3-4 GVHD	18 percentage of participants	—

SECONDARY outcome

Timeframe: 100 days

Toxicity of etanercept was evaluated by the following: the number of patients experiencing allergic reactions, the number of patients that discontinued etanercept early, the number of patients experiencing bacteremia, and the number of patients experiencing viral reactivations.

Outcome measures

Outcome measures
Measure	GVHD Prophylaxis n=100 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.	Non-TBI GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Number of Patients Experiencing Etanercept Toxicity Number of Patients Experiencing Viral Reactivation	24 participants	—
Number of Patients Experiencing Etanercept Toxicity Number of Patients Experiencing Allergic Reactions	0 participants	—
Number of Patients Experiencing Etanercept Toxicity Number of Patients that Discontinued Drug Early	5 participants	—
Number of Patients Experiencing Etanercept Toxicity Number of Patients Experiencing Bacteremia	59 participants	—

SECONDARY outcome

Timeframe: 100 days

Population: TBI versus Non-TBI transplant conditioning

The Effect of etanercept on the incidence of idiopathic pulmonary syndrome (IPS). Patients who received Total Body Irradiation (TBI) transplant conditioning were compared to those who received another form of transplant conditioning.

Outcome measures

Outcome measures
Measure	GVHD Prophylaxis n=29 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.	Non-TBI n=71 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day+7, post transplant

Population: TBI versus non-TBI transplant conditioning

The effect of etanercept on plasma cytokine levels after Hematopoietic Stem Cell Transplantation (HSCT) was analyzed. Tumor Necrosis Factor Receptor 1 (TNFR1) ratios (TNFR1 posttransplantation day+7 / TNFR1pretransplantation baseline were calculated. Patients who received Total Body Irradiation (TBI) transplant conditioning were compared to those who received another form of transplant conditioning.

Outcome measures

Outcome measures
Measure	GVHD Prophylaxis n=29 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.	Non-TBI n=71 Participants GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients	1.89 TNFR1 Ratio Interval 1.07 to 5.15	1.1 TNFR1 Ratio Interval 0.41 to 5.47

SECONDARY outcome

Timeframe: 100 days

Population: This was not analyzed in the population and there are no plans to analyze this in the future. The study is complete and the principal investigator has left the institution.

Outcome measures

Outcome data not reported

Adverse Events

GVHD Prophylaxis

Serious events: 25 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GVHD Prophylaxis n=100 participants at risk GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome (ARDS)	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Immune system disorders Allergic Reaction / Hypersensitivity	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Blood and lymphatic system disorders Blood Bone Marrow - Other	2.0% 2/100 • Number of events 2 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders CNS Cerebrovascular Ischemia	1.0% 1/100 • Number of events 2 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Catheter - Related Infection	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders Depressed Level of Consciousness	2.0% 2/100 • Number of events 2 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Diarrhea	6.0% 6/100 • Number of events 9 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Renal and urinary disorders Dysuria	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hyperglycemia	3.0% 3/100 • Number of events 3 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypernatremia	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypoalbuminemia	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypocalcemia	2.0% 2/100 • Number of events 2 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypomagnesemia	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Vascular disorders Hypotension	3.0% 3/100 • Number of events 3 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 4/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Infection wtih Unknown ANC	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Infection without Neutropenia	6.0% 6/100 • Number of events 7 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Nausea	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Psychiatric disorders Personality / Behavioral	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Skin and subcutaneous tissue disorders Rash / Desquamation	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders Seizure	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Reproductive system and breast disorders Sexual / Reproductive Function	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders Syncope	2.0% 2/100 • Number of events 2 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Vascular disorders Thrombosis / Embolism	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Renal and urinary disorders Ureteral Obstruction	1.0% 1/100 • Number of events 1 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.

Other adverse events

Other adverse events
Measure	GVHD Prophylaxis n=100 participants at risk GVHD prophylaxis with etanercept Etanercept : Etanercept 0.4 mg/kg per dose \[maximum dose 25 mg\] SC for prophylaxis. To start in the 24 hour time period along with the initiation of the preparative regimen for the stem cell transplant. Etanercept will be administered twice weekly until day +56 (8 weeks) post transplant.
Gastrointestinal disorders Abdominal Pain or Cramping	8.0% 8/100 • Number of events 9 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Anorexia	24.0% 24/100 • Number of events 29 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Psychiatric disorders Confusion	10.0% 10/100 • Number of events 12 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
General disorders Constitutional Symptoms - Other	7.0% 7/100 • Number of events 10 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders Depressed Level of Consciousness	5.0% 5/100 • Number of events 5 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Diarrhea	8.0% 8/100 • Number of events 8 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Dysphagia	5.0% 5/100 • Number of events 5 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.0% 16/100 • Number of events 17 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
General disorders Edema	11.0% 11/100 • Number of events 12 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.0% 12/100 • Number of events 13 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
General disorders Fatigue	14.0% 14/100 • Number of events 14 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Blood and lymphatic system disorders Febrile Neutropenia	24.0% 24/100 • Number of events 24 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Psychiatric disorders Hallucinations	10.0% 10/100 • Number of events 10 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Nervous system disorders Headache	6.0% 6/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hyperglycemia	30.0% 30/100 • Number of events 50 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hyperkalemia	7.0% 7/100 • Number of events 8 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Vascular disorders Hypertension	24.0% 24/100 • Number of events 29 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypoalbuminemia	10.0% 10/100 • Number of events 11 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypocalcemia	15.0% 15/100 • Number of events 15 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypokalemia	18.0% 18/100 • Number of events 22 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hyponatremia	11.0% 11/100 • Number of events 11 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Metabolism and nutrition disorders Hypophosphatemia	7.0% 7/100 • Number of events 7 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Vascular disorders Hypotension	22.0% 22/100 • Number of events 22 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Hypoxia	30.0% 30/100 • Number of events 35 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Infection with Grade 3 or 4 Neutropenia	11.0% 11/100 • Number of events 11 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Psychiatric disorders Mood Alteration - Anxiety, Agitation	8.0% 8/100 • Number of events 9 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Psychiatric disorders Mood Alteration - Depression	12.0% 12/100 • Number of events 12 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Musculoskeletal and connective tissue disorders Muscle Weakness	11.0% 11/100 • Number of events 11 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Nausea	9.0% 9/100 • Number of events 9 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
General disorders Pain - Other	5.0% 5/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	5.0% 5/100 • Number of events 5 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Respiratory, thoracic and mediastinal disorders Pneumonitis / Pulmonary Infiltrates	6.0% 6/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Skin and subcutaneous tissue disorders Rash / Desquamation	8.0% 8/100 • Number of events 8 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Renal and urinary disorders Renal Failure	6.0% 6/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Investigations AST High	6.0% 6/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Investigations ALT High	11.0% 11/100 • Number of events 11 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Cardiac disorders Sinus Tachycardia	8.0% 8/100 • Number of events 9 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Stomatitis Pharyngitis	18.0% 18/100 • Number of events 19 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Infections and infestations Stomatitis Pharyngitis BMT	6.0% 6/100 • Number of events 6 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Gastrointestinal disorders Vomiting	5.0% 5/100 • Number of events 5 • Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.

Additional Information

Dr. John E. Levine

Blood and Marrow Transplant Program, University of Michigan

Phone: 734-936-8456

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place