A Phase 2 interventional study of Etanercept in Graft-Versus-Host Disease, sponsored by University of Michigan Rogel Cancer Center. Completed at 2 sites in United States. Open to participants aged 1 Year to 60 Years. Per ClinicalTrials.gov, last updated 2017-01-30.
Sponsored by University of Michigan Rogel Cancer Center · Phase 2, Interventional, and Treatment
This is a clinical trial to see if the addition of etanercept to standard preventative medicines helps in preventing two major complications of hematopoietic stem cell transplantation (HSCT): decrease the rate of acute graft-vs-host disease (GVHD) and the risk of death.
This is a clinical trial to see if the addition of etanercept helps in preventing two major complications of hematopoietic stem cell transplantation (HSCT). The main objective will be to see whether the addition of etanercept to standard preventative medicines will decrease the rate of acute graft-vs-host disease (GVHD) and the risk of death by 100 days following allogeneic HSCT from volunteer donors.
GVHD is a common complication following a bone marrow transplant from another donor. GVHD occurs after transplant when the donor's blood cells recognize parts of the body as foreign. During this process, chemicals called cytokines are released that may damage certain body tissues, including the gut, liver and skin. Some of the main effects can include red skin rash, diarrhea, sometimes with blood, and yellow jaundice. It can range from mild to life threatening and often requires admission to the hospital for treatment. The standard treatment for acute GVHD is a combination of steroids and another drug that suppress the immune system, such as tacrolimus or cyclosporine.
Etanercept is a drug that blocks a chemical called Tumor Necrosis Factor (TNF) from causing damage to your tissue. The purpose of etanercept is to help improve the response to standard treatment for GVHD. Previous studies have shown that less than 50% of patients respond fully to GVHD treatment. Without a good response, patients often have a prolonged treatment for this disease, often involving hospitalization and sometimes even death. Etanercept (Enbrel) will be added to the standard treatment to see if we can lower the rate of GVHD and the risk of death from GVHD by blocking TNF.
806 studies on the registry are indexed under Graft vs Host Disease; 138 are open to participants now.
This study's enrollment of 100 is above the median of 35 across 637 interventional studies indexed under Graft vs Host Disease.
Browse Graft vs Host Disease studies →University of Michigan Rogel Cancer Center is the lead sponsor of 316 studies on the registry; 46 are open to participants now.
Of its 46 completed or terminated interventional studies of FDA-regulated products, 30 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
GVHD prophylaxis with etanercept
Drug: 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.
Also known as: Enbrel
The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
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
Number of Patients Experiencing Etanercept Toxicity
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
The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)
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.
Time frame: 100 days
Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients
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
The Impact of Tumor Necrosis Factor (TNF) Polymorphisms on Response to Therapy.
Time frame: 100 days
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.
| Milestone | GVHD Prophylaxis |
|---|---|
| Started | 100 |
| Completed | 100 |
| Not completed | 0 |
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
| percentage of participants | GVHD Prophylaxis |
|---|---|
| Incidence of Grades 2-4 GVHD | 45 (95 to 105) |
| Incidence of Grades 3-4 GVHD | 18 |
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.
| participants | GVHD Prophylaxis |
|---|---|
| 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 |
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.
| Participants | Total Body Irradiation (TBI) | Non-TBI |
|---|---|---|
| The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS) | 1 | 0 |
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.
| TNFR1 Ratio | Total Body Irradiation (TBI) | Non-TBI |
|---|---|---|
| Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients | 1.89 (1.07 to 5.15) | 1.1 (0.41 to 5.47) |
No measurements were reported for this outcome.
Collected over Adverse Events (AEs) were collected from the first dose of study drug until day +100 post transplant.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| GVHD Prophylaxis | — | 25/100 (25%) | 89/100 (89%) |
| Event | GVHD Prophylaxis |
|---|---|
| DiarrheaGastrointestinal disorders | 6/100 |
| Infection without NeutropeniaInfections and infestations | 6/100 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 4/100 |
| HyperglycemiaMetabolism and nutrition disorders | 3/100 |
| HypotensionVascular disorders | 3/100 |
| Blood Bone Marrow - OtherBlood and lymphatic system disorders | 2/100 |
| Depressed Level of ConsciousnessNervous system disorders | 2/100 |
| HypocalcemiaMetabolism and nutrition disorders | 2/100 |
| SyncopeNervous system disorders | 2/100 |
| Adult Respiratory Distress Syndrome (ARDS)Respiratory, thoracic and mediastinal disorders | 1/100 |
| Event | GVHD Prophylaxis |
|---|---|
| HyperglycemiaMetabolism and nutrition disorders | 30/100 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 30/100 |
| AnorexiaMetabolism and nutrition disorders | 24/100 |
| Febrile NeutropeniaBlood and lymphatic system disorders | 24/100 |
| HypertensionVascular disorders | 24/100 |
| HypotensionVascular disorders | 22/100 |
| HypokalemiaMetabolism and nutrition disorders | 18/100 |
| Stomatitis PharyngitisInfections and infestations | 18/100 |
| DyspneaRespiratory, thoracic and mediastinal disorders | 16/100 |
| HypocalcemiaMetabolism and nutrition disorders | 15/100 |
| Age, Continuous(years) | GVHD Prophylaxis |
|---|---|
| Median | 47 ± 5 |
| Gender(Participants) | GVHD Prophylaxis |
|---|---|
| Female | 43 |
| Male | 57 |
| Region of Enrollment(participants) | GVHD Prophylaxis |
|---|---|
| United States | 100 |
| Disease status at transplantation(participants) | GVHD Prophylaxis |
|---|---|
| Low risk | 39 |
| Intermediate risk | 33 |
| High risk | 28 |
| Donor match(participants) | GVHD Prophylaxis |
|---|---|
| 8/8 matched unrelated | 71 |
| 7/8 mismatched unrelated | 26 |
| 7/8 mismatched related | 3 |
| Conditioning Regimen Parameter(participants) | GVHD Prophylaxis |
|---|---|
| Non-Total body radiation | 71 |
| Total body radiation | 29 |
This study is completed, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.
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University of Michigan Rogel Cancer Center