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

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ClinicalTrials.gov Identifier: NCT00141739
Recruitment Status : Completed
First Posted : September 1, 2005
Results First Posted : June 4, 2014
Last Update Posted : January 30, 2017
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Graft-Versus-Host Disease
Intervention Drug: Etanercept
Enrollment 100
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title GVHD Prophylaxis
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 100 [1]
Completed 100
Not Completed 0
[1]
Number of evaluable patients
Arm/Group Title GVHD Prophylaxis
Hide Arm/Group Description

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 Number of Baseline Participants 100
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 100 participants
47
(2 to 61)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants
Female
43
  43.0%
Male
57
  57.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 100 participants
100
Disease status at transplantation   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants
Low risk 39
Intermediate risk 33
High risk 28
[1]
Measure Description: Disease classifications correspond to the Center for International Blood and Marrow Transplant Research Request for Information Disease Classifications Form (www.cibmtr.org).
Donor match  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants
8/8 matched unrelated 71
7/8 mismatched unrelated 26
7/8 mismatched related 3
Conditioning Regimen Parameter   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 100 participants
Non-Total body radiation 71
Total body radiation 29
[1]
Measure Description: Those subjects that did or did not receive Total body irradiation as part of their conditioning regimen.
1.Primary Outcome
Title The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Hide Description

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

Time Frame 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
To provide Sufficient power
Arm/Group Title GVHD Prophylaxis
Hide Arm/Group Description:

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 Number of Participants Analyzed 100
Measure Type: Number
Unit of Measure: percentage of participants
Incidence of Grades 2-4 GVHD 45
Incidence of Grades 3-4 GVHD 18
2.Secondary Outcome
Title Number of Patients Experiencing Etanercept Toxicity
Hide Description 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.
Time Frame 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GVHD Prophylaxis
Hide Arm/Group Description:

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 Number of Participants Analyzed 100
Measure Type: Number
Unit of Measure: participants
Number of Patients Experiencing Allergic Reactions 0
Number of Patients that Discontinued Drug Early 5
Number of Patients Experiencing Bacteremia 59
Number of Patients Experiencing Viral Reactivation 24
3.Secondary Outcome
Title The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)
Time Frame 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
TBI versus Non-TBI transplant conditioning
Arm/Group Title Total Body Irradiation (TBI) Non-TBI
Hide Arm/Group Description:

GVHD prophylaxis with etanercept in patients receiving Total Body Irradiation (TBI) transplant conditioning.

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.

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 Number of Participants Analyzed 29 71
Measure Type: Count of Participants
Unit of Measure: Participants
1
   3.4%
0
   0.0%
4.Secondary Outcome
Title Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients
Hide Description 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.
Time Frame Day+7, post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
TBI versus non-TBI transplant conditioning
Arm/Group Title Total Body Irradiation (TBI) Non-TBI
Hide Arm/Group Description:

GVHD prophylaxis with etanercept in patients receiving Total Body Irradiation (TBI) transplant conditioning.

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.

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 Number of Participants Analyzed 29 71
Mean (Full Range)
Unit of Measure: TNFR1 Ratio
1.89
(1.07 to 5.15)
1.1
(0.41 to 5.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Total Body Irradiation (TBI), Non-TBI
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments Wilcoxon rank sum test
5.Secondary Outcome
Title The Impact of Tumor Necrosis Factor (TNF) Polymorphisms on Response to Therapy.
Hide Description [Not Specified]
Time Frame 100 days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Total Body Irradiation (TBI) Non-TBI
Hide Arm/Group Description:

GVHD prophylaxis with etanercept in patients receiving Total Body Irradiation (TBI) transplant conditioning.

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.

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 Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title GVHD Prophylaxis
Hide Arm/Group Description

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.

All-Cause Mortality
GVHD Prophylaxis
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
GVHD Prophylaxis
Affected / at Risk (%) # Events
Total   25/100 (25.00%)    
Blood and lymphatic system disorders   
Blood Bone Marrow - Other  2/100 (2.00%)  2
Gastrointestinal disorders   
Diarrhea  6/100 (6.00%)  9
Nausea  1/100 (1.00%)  1
Immune system disorders   
Allergic Reaction / Hypersensitivity  1/100 (1.00%)  1
Infections and infestations   
Catheter - Related Infection  1/100 (1.00%)  1
Infection wtih Unknown ANC  1/100 (1.00%)  1
Infection without Neutropenia  6/100 (6.00%)  7
Metabolism and nutrition disorders   
Hyperglycemia  3/100 (3.00%)  3
Hypernatremia  1/100 (1.00%)  1
Hypoalbuminemia  1/100 (1.00%)  1
Hypocalcemia  2/100 (2.00%)  2
Hypomagnesemia  1/100 (1.00%)  1
Nervous system disorders   
CNS Cerebrovascular Ischemia  1/100 (1.00%)  2
Depressed Level of Consciousness  2/100 (2.00%)  2
Seizure  1/100 (1.00%)  1
Syncope  2/100 (2.00%)  2
Psychiatric disorders   
Personality / Behavioral  1/100 (1.00%)  1
Renal and urinary disorders   
Dysuria  1/100 (1.00%)  1
Ureteral Obstruction  1/100 (1.00%)  1
Reproductive system and breast disorders   
Sexual / Reproductive Function  1/100 (1.00%)  1
Respiratory, thoracic and mediastinal disorders   
Adult Respiratory Distress Syndrome (ARDS)  1/100 (1.00%)  1
Dyspnea  1/100 (1.00%)  1
Hypoxia  4/100 (4.00%)  6
Skin and subcutaneous tissue disorders   
Rash / Desquamation  1/100 (1.00%)  1
Vascular disorders   
Hypotension  3/100 (3.00%)  3
Thrombosis / Embolism  1/100 (1.00%)  1
1
Term from vocabulary, CTCAE (2.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GVHD Prophylaxis
Affected / at Risk (%) # Events
Total   89/100 (89.00%)    
Blood and lymphatic system disorders   
Febrile Neutropenia  24/100 (24.00%)  24
Cardiac disorders   
Sinus Tachycardia  8/100 (8.00%)  9
Gastrointestinal disorders   
Abdominal Pain or Cramping  8/100 (8.00%)  9
Diarrhea  8/100 (8.00%)  8
Dysphagia  5/100 (5.00%)  5
Nausea  9/100 (9.00%)  9
Vomiting  5/100 (5.00%)  5
General disorders   
Constitutional Symptoms - Other  7/100 (7.00%)  10
Edema  11/100 (11.00%)  12
Fatigue  14/100 (14.00%)  14
Pain - Other  5/100 (5.00%)  6
Infections and infestations   
Infection with Grade 3 or 4 Neutropenia  11/100 (11.00%)  11
Stomatitis Pharyngitis  18/100 (18.00%)  19
Stomatitis Pharyngitis BMT  6/100 (6.00%)  6
Investigations   
AST High  6/100 (6.00%)  6
ALT High  11/100 (11.00%)  11
Metabolism and nutrition disorders   
Anorexia  24/100 (24.00%)  29
Hyperglycemia  30/100 (30.00%)  50
Hyperkalemia  7/100 (7.00%)  8
Hypoalbuminemia  10/100 (10.00%)  11
Hypocalcemia  15/100 (15.00%)  15
Hypokalemia  18/100 (18.00%)  22
Hyponatremia  11/100 (11.00%)  11
Hypophosphatemia  7/100 (7.00%)  7
Musculoskeletal and connective tissue disorders   
Muscle Weakness  11/100 (11.00%)  11
Nervous system disorders   
Depressed Level of Consciousness  5/100 (5.00%)  5
Headache  6/100 (6.00%)  6
Psychiatric disorders   
Confusion  10/100 (10.00%)  12
Hallucinations  10/100 (10.00%)  10
Mood Alteration - Anxiety, Agitation  8/100 (8.00%)  9
Mood Alteration - Depression  12/100 (12.00%)  12
Renal and urinary disorders   
Renal Failure  6/100 (6.00%)  6
Respiratory, thoracic and mediastinal disorders   
Dyspnea  16/100 (16.00%)  17
Epistaxis  12/100 (12.00%)  13
Hypoxia  30/100 (30.00%)  35
Pleural Effusion  5/100 (5.00%)  5
Pneumonitis / Pulmonary Infiltrates  6/100 (6.00%)  6
Skin and subcutaneous tissue disorders   
Rash / Desquamation  8/100 (8.00%)  8
Vascular disorders   
Hypertension  24/100 (24.00%)  29
Hypotension  22/100 (22.00%)  22
1
Term from vocabulary, CTCAE (2.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. John E. Levine
Organization: Blood and Marrow Transplant Program, University of Michigan
Phone: 734-936-8456
Responsible Party: University of Michigan Rogel Cancer Center
ClinicalTrials.gov Identifier: NCT00141739     History of Changes
Other Study ID Numbers: UMCC 2004.008
First Submitted: August 30, 2005
First Posted: September 1, 2005
Results First Submitted: January 21, 2014
Results First Posted: June 4, 2014
Last Update Posted: January 30, 2017