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

Condition(s) targeted: Graft-Versus-Host Disease

Intervention: Etanercept (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Michigan Cancer Center

Official(s) and/or principal investigator(s):
John E. Levine, MD, MS, Principal Investigator, Affiliation: The University of Michigan Comprehensive Cancer Center

Overall contact:
John E. Levine, MD, MS, Phone: 734-936-8785

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.

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 design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Primary outcome: To determine whether etanercept given prophylactically, along with a standard GVHD prevention regimen, will decrease the 100-day mortality and the rate of acute GVHD after allogeneic hematopoietic stem cell transplantation(HSCT)

Secondary outcome:

Evaluation of, the toxicity profile of etanercept when given in this clinical context

the effect of etanercept on the incidence of idiopathic pulmonary syndrome (IPS)

the effect of etanercept on plasma and cellular cytokine levels after HSCT

and the impact of tumor necrosis factor (TNF) polymorphisms on response to therapy.

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.

Minimum age: 1 Year. Maximum age: 60 Years. Gender(s): Both.

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.

John E. Levine, MD, MS, Phone: 734-936-8785

Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, Illinois 60153, United States; Recruiting
Mary Lee, RN, BSN, Phone: 708-327-2241, Email: mlee@lumc.edu
Patrick Stiff, MD, Principal Investigator

The University of Michigan, Ann Arbor, Michigan 48109, United States; Recruiting
Cancer AnswerLine, Phone: 800-865-1125
Cancer AnswerLine, Phone: 1-800-865-1125
John E. Levine, MS MD, Principal Investigator

Starting date: August 2004
Ending date: August 2010
Last updated: July 13, 2009