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

NCT ID: NCT00141739

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2012-09-30

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.

Conditions

Graft-Versus-Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GVHD prophylaxis

GVHD prophylaxis with etanercept

Group Type: EXPERIMENTAL

Etanercept

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Enbrel

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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John E. Levine, MD, MS

Role: PRINCIPAL_INVESTIGATOR

The University of Michigan Comprehensive Cancer Center

Locations

Loyola University Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, United States

The University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 22469883 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22155140 (View on PubMed)

Other Identifiers

UMCC 2004.008

Identifier Type: -

Identifier Source: org_study_id