Clinical trial NCT00141739: Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT)
Official title: The Addition of Etanercept to Standard GVHD Prophylaxis in Patients Undergoing a Full Intensity Allogeneic Hematopoietic Stem Cell Transplant for the Prevention of Transplant Related Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Graft-Versus-Host Disease
Keywords: Stem Cell Transplantation
Graft-Versus-Host Disease
prophylaxis
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2005-09-01
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
timeFrame: 100 days
Secondary outcomes:
measure: Number of Patients Experiencing Etanercept Toxicity
timeFrame: 100 days
measure: The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)
timeFrame: 100 days
measure: Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients
timeFrame: Day+7, post transplant
measure: The Impact of Tumor Necrosis Factor (TNF) Polymorphisms on Response to Therapy.
timeFrame: 100 days
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center, Cardinal Bernardin Cancer Center
state: Illinois
city: Ann Arbor
country: United States
facility: The University of Michigan
state: Michigan
Study officials:
affiliation: The University of Michigan Comprehensive Cancer Center
name: John E. Levine, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Choi SW, Stiff P, Cooke K, Ferrara JL, Braun T, Kitko C, Reddy P, Yanik G, Mineishi S, Paczesny S, Hanauer D, Pawarode A, Peres E, Rodriguez T, Smith S, Levine JE. TNF-inhibition with etanercept for graft-versus-host disease prevention in high-risk HCT: lower TNFR1 levels correlate with better outcomes. Biol Blood Marrow Transplant. 2012 Oct;18(10):1525-32. doi: 10.1016/j.bbmt.2012.03.013. Epub 2012 Mar 30.
citation: Yanik GA, Mineishi S, Levine JE, Kitko CL, White ES, Vander Lugt MT, Harris AC, Braun T, Cooke KR. Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute pulmonary dysfunction following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2012 Jul;18(7):1044-54. doi: 10.1016/j.bbmt.2011.11.031. Epub 2011 Dec 10.