Effectiveness of Etanercept for Idiopathic Pneumonia Syndrome Following Stem Cell Transplantation (BMT CTN 0403)
Condition: Pneumonia; Idiopathic Pneumonia Syndrome
MeSH terms: Pneumonia; Syndrome
Intervention: Etanercept; Placebo plus corticosteroid
Intervention description: Etanercept will be given eight doses of study drug over a 4-week period. The initial dose of etanercept will be administered intravenously on Day 0, with subsequent doses administered subcutaneously (SQ). Dosing will be administered twice weekly over 4 consecutive weeks. Additionally, patients in both arms will receive corticosteroids (2 mg/kg/day) Day 0 through Day 7, with subsequent taper as clinically indicated.; Patients will receive a total of eight doses of placebo over a 4-week period. The initial dose of placebo will be administered intravenously on Day 0, with subsequent doses administered subcutaneously (SQ). Dosing will be administered twice weekly over 4 consecutive weeks. The placebo will be the inert diluent used for the etanercept formulation.
Additionally, patients in both arms will receive corticosteroids (2 mg/kg/day) Day 0 through Day 7, with subsequent taper as clinically indicated.
Intervention MeSH terms: Methylprednisolone; Etanercept
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Etanercept; IPS

Summary:

      The study is designed as a Phase III, multi-center randomized, double-blind,
      placebo-controlled trial investigating the use of etanercept for the treatment of acute,
      non-infectious pulmonary dysfunction (IPS) occurring after allogeneic hematopoietic cell
      transplantation (HCT).
    

Eligibility criteria:

        Inclusion Criteria:

        Patients fulfilling the following criteria will be eligible for registration in this study:

          -  Recipient of an allogeneic bone marrow, cord blood, or peripheral blood stem cell
             transplant. There are no restrictions based upon underlying disease, donor source,
             degree of human leukocyte antigen (HLA) match, intensity of the pre-transplant
             conditioning regimen, or the use of a prior donor leukocyte infusion

          -  Evidence of acute lung injury, based upon the presence of bilateral pulmonary
             infiltrates (on chest radiograph) and a supplemental oxygen requirement

          -  No more than 180 days post transplant

        Patients fulfilling the following criteria will be eligible for random assignment in this
        study:

          -  BAL fluid negative for pathogenic microorganisms as assessed by gram stain and fungal
             stain

          -  BAL fluid negative for pathogenic microorganisms, or test result pending, as assessed
             by the following tests:

               1. Acid fast bacilli stain (AFB)

               2. Bacterial culture (a quantitative culture of at least 10(4) CFU/mL is considered
                  positive)

               3. Viral cultures for respiratory pathogens, including Respiratory syncytial virus
                  (RSV), adenovirus, parainfluenza, influenza A and B, and Cytomegalovirus (CMV)

               4. Fungal and mycobacterial cultures

               5. Pneumocystis carinii pneumonia (PCP) assay, by polymerase chain reaction (PCR),
                  direct fluorescent antibody (DFA) stain, or cytology (per institutional
                  guidelines)

        Exclusion Criteria:

          -  Sepsis syndrome or hypotension in which inotropic support (excluding dopamine of no
             more than 5 mcg/kg/minute) is required

          -  Bacteremia within 48 hours prior to study registration

          -  Documented invasive fungal or systemic viral infection (excluding asymptomatic
             viruria) within 14 days prior to study registration

          -  Evidence of CMV infection, based upon an abnormal PCR assay, antigenemia assay, or
             shell vial culture within 14 days of study registration

          -  On mechanical ventilation for more than 48 hours at study registration

          -  Evidence of congestive heart failure by clinical assessment

          -  Participating in other investigational studies (Phase I, II, or III) for the treatment
             of acute GVHD within 7 days of study registration (patients enrolled in BMT CTN 0302
             are ineligible for study entry)

          -  Received etanercept within 14 days prior to study registration

          -  Pregnant or breastfeeding

          -  On more than 2 mg/kg/day of methylprednisolone equivalent for more than 48 hours,
             within 7 days prior to study registration

          -  Known hypersensitivity to etanercept

          -  History of active tuberculosis (TB) infection

          -  History of chronic active hepatitis B or hepatitis C infection

          -  Patients who have undergone a BAL within 72 hours of study registration are ineligible
             if the BAL fluid is known to be positive for pathogenic microorganisms

          -  Patients who have relapsed or have developed progressive disease post-transplant