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

Phase 2

Completed

Conditions: Graft-Versus-Host Disease

Interventions: Drug: Etanercept

Registration Number: NCT00141739

Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 100

Inclusion Criteria

Patients must be between 1 and 60 years of age and be a candidate for myeloablative donor stem cell transplantation
Patients must receive myeloablative regimen using fludarabine and busulfan
For related donors: The donor and recipient must have a 5/6 match at the HLA A, B, and DRB1 loci. [Patients with a 6/6 related donor are NOT eligible.] For unrelated donors: The donor and recipient must have a 5/6 or 6/6 match at the HLA A, B, and DRB1 loci.
The typing level to define a match at the A and B locus must be at the level of mid-resolution DNA typing. The acceptable level to define a match at DRB1 will be by allelic typing by high resolution DNA sequencing.
Any disease for which myeloablative transplantation is appropriate is eligible except: Progressive or poorly controlled malignancies for which the likelihood of durable disease control [i.e., patients expected to have at least 6 months PFS from date of transplant] is <25%.

Exclusion Criteria

Not a candidate for myeloablative conditioning regimen using the current BMT program clinical guidelines.
Patient has a 6/6 HLA-matched related donor
Karnofsky or Lansky performance status of < 60% at the time of admission for HSCT
Patients with evidence of HIV infection or other opportunistic infection including but not limited to tuberculosis and histoplasmosis.
Any conditions, in the opinion of the transplant team such as substance abuse, or severe personality disorder that would keep the patients from complying with the needs of the protocol and would markedly increase the morbidity and mortality from the procedure.
Pregnancy.
T-cell depleted allograft
Patients with documented infections, not responding well to antibiotic therapy.
Patients with bacteremia.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GVHD prophylaxis	Etanercept	GVHD prophylaxis with etanercept

Primary Outcome Measures

Name	Time	Method
The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)	100 days	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

Secondary Outcome Measures

Name	Time	Method
Number of Patients Experiencing Etanercept Toxicity	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.
The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)	100 days	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.
Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients	Day+7, post transplant	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.
The Impact of Tumor Necrosis Factor (TNF) Polymorphisms on Response to Therapy.	100 days

Trial Locations

Locations (2): Loyola University Medical Center, Cardinal Bernardin Cancer Center
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Maywood, Illinois, United States
The University of Michigan
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Ann Arbor, Michigan, United States