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

NCT00141739 | Completed Phase 2 Results DMC

• 1 other identifier: UMCC 2004.008
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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.

Conditions

Graft-Versus-Host Disease

Keywords

Stem Cell Transplantation; Graft-Versus-Host Disease; prophylaxis

Outcome Measures

Primary Outcomes (1)

• 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

  100 days

Secondary Outcomes (4)

• Number of Patients Experiencing Etanercept Toxicity

  100 days

• The Number of Patients That Experience Idiopathic Pulmonary Syndrome (IPS)

  100 days

• Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients

  Day+7, post transplant

• The Impact of Tumor Necrosis Factor (TNF) Polymorphisms on Response to Therapy.

  100 days

Study Arms (1)

GVHD prophylaxis

EXPERIMENTAL

GVHD prophylaxis with etanercept

Drug: Etanercept

Interventions

Etanercept 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.

Also known as: Enbrel

GVHD prophylaxis

Eligibility Criteria

• Age: 1 Year - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead

Study Sites (2)

Loyola University Medical Center, Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

The University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (2)

• 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.

  PMID: 22469883 BACKGROUND

• 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.

  PMID: 22155140 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Dr. John E. Levine
• Organization: Blood and Marrow Transplant Program, University of Michigan

jelevine@med.umich.edu

734-936-8456

Study Officials

• John E. Levine, MD, MS

  The University of Michigan Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2005
• First Posted: September 1, 2005
• Study Start: August 1, 2004
• Primary Completion: August 1, 2011
• Study Completion: September 1, 2012
• Last Updated: January 30, 2017
• Results First Posted: June 4, 2014

Record last verified: 2016-12

Locations

US (2)