Clinical trial NCT01432080: Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant
Official title: Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Respiratory Tract Infections
Bronchiolitis Obliterans
Cryptogenic Organizing Pneumonia
Lung Diseases, Interstitial
Keywords: Pulmonary disease, chronic obstructive
Viral respiratory tract infections
Respiratory syncytial viruses
Influenza virus A
Influenza virus B
Transplantation, Allogeneic
Lead sponsor: Maisonneuve-Rosemont Hospital
Sponsor class: OTHER
Collaborators: name: The Canadian Blood and Marrow Transplant Group
First posted: 2011-09-12
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: For many patients with blood cancers, stem cell transplantation from a family member or from an unrelated donor remains the only potentially curative option. Unfortunately, up to 40% of patients develop chronic lung disease after the transplant, which substantially increases the risk of death in the long-term. Currently, patients with transplant-related lung disease are treated with some combination of steroids and other immunosuppressant drugs, but only about 1 out of 5 improve.

The importance of our study is that the investigators aim to prevent the development of transplant-related chronic lung disease in the first place. Because a strong risk factor for such chronic lung disease is a prior viral respiratory tract infection, the investigators think there is a window of opportunity to intervene. As soon as "cold and flu" symptoms start, the investigators will treat patients with a combination of drugs aimed at eliminating damaging immune responses triggered by the virus. In the absence of such treatment, the investigators believe these lung-damaging immune responses would persist even after the virus disappears. Our hope is that preventive treatment might avoid the development of chronic lung disease, and this would substantially increase long-term survival in our transplant patients.

This is a pilot study. Once feasibility is established, the investigators will seek to expand this study into a definitive clinical trial.


Eligibility criteria: Inclusion Criteria:

* Allogeneic transplant within the prior 1 year
* Age greater than or equal to 18 years
* Capable of informed consent
* Neutrophil engraftment has occurred
* This is the first clinically-recognized episode of viral respiratory tract infection after transplant

Exclusion Criteria:

* Proof or high suspicion for bacterial, fungal or any non-viral microorganism causing pneumonia
* CMV, VZV or HSV pneumonia
* Prior diagnosis of a chronic transplant-related non-infectious pulmonary complication (ex: BO, COP)
* Treating physician believes the risk of systemic steroids is too great
* Currently receiving prednisone at or greater than 0.25 mg/kg/day or the equivalent dose of another steroid
* Currently receiving pentostatin
* Mycophenolate initiated de novo or increased within the past 4 weeks
* Use of inhaled corticosteroids within the past 2 weeks for at least 1 week
* Haploidentical or T-cell depleted graft
* Lack of pre-transplant pulmonary function tests
* Evidence of a prior symptomatic viral respiratory tract infection following transplant, whether treated or not
* Allergy or adverse reaction to any of the study drugs
* Relapse or progression of the underlying malignancy
* Palliative care

Primary outcomes:
measure: Cumulative incidence of new chronic lung disease
timeFrame: 6 months following diagnosis of the viral respiratory tract infection
Secondary outcomes:
measure: Prevalence of non-infectious pulmonary complications
timeFrame: 6 months following the diagnosis of viral respiratory tract infection
measure: Long-term functional impairment as defined by need for supplemental oxygen
timeFrame: 6 months post viral respiratory tract infection
measure: Patient-perceived long-term functional impairment
timeFrame: 6 months post viral respiratory tract infection
measure: Time to clearance of viral infection
timeFrame: Every 2 weeks until virus is no longer detectable
measure: Incidence of progression to respiratory failure
timeFrame: 21 days after enrolment
measure: Incidence of bacterial or fungal superinfection
timeFrame: Within 21 days after enrolment
measure: Incidence of various other infectious complications
timeFrame: Within 6 months after enrolment
measure: Overall survival from date of viral respiratory tract infection
timeFrame: 3 months post enrolment
measure: Overall survival from date of viral respiratory tract infection
timeFrame: 6 months post enrolment
measure: Overall survival from date of transplant to end of study follow-up
timeFrame: 6 months post enrolment
measure: Overall survival at 1 year post-transplant
timeFrame: 1 year post-transplant
measure: Cumulative incidence of death attributable to transplant associated lung disease
timeFrame: 6 months post enrolment
measure: Cumulative incidence of death from other causes
timeFrame: 6 months post enrolment
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont)
state: Quebec
Study officials:
affiliation: Maisonneuve-Rosemont Hospital
name: Elizabeth F Krakow, MD,CM, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Maisonneuve-Rosemont Hospital
name: Sandra Cohen, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: