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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Levine, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00141739
First received: August 30, 2005
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Graft-Versus-Host Disease
Drug: Etanercept
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

    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:
  • Number of Patients Experiencing Etanercept Toxicity [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    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 Effect of Etanercept on the Incidence of Idiopathic Pulmonary Syndrome (IPS) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Day +7 TNFR1 Ratio in TBI-Treated Patients vs. Non-TBI-Treated Patients [ Time Frame: Day+7, post transplant ] [ Designated as safety issue: No ]
    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 at Day+7 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. [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Enrollment: 100
Study Start Date: August 2004
Study Completion Date: September 2012
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GVHD prophylaxis
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.

Other Name: Enbrel

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

Ages Eligible for Study:   1 Year to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00141739

Locations
United States, Illinois
Loyola University Medical Center, Cardinal Bernardin Cancer Center
Maywood, Illinois, United States, 60153
United States, Michigan
The University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: John E. Levine, MD, MS The University of Michigan Comprehensive Cancer Center
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: John Levine, MD, Professor of Pediatrics, and of Internal Medicine, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00141739     History of Changes
Other Study ID Numbers: UMCC 2004.008
Study First Received: August 30, 2005
Results First Received: January 21, 2014
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
Stem Cell Transplantation
Graft-Versus-Host Disease
prophylaxis

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 01, 2014