Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant

Phase 2TerminatedNCT01432080

Maisonneuve-Rosemont Hospital12 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Respiratory Tract Infections

Interventions

PrednisoneDRUG

Prednisone 0.75 mg/kg actual body weight/day PO for 7 days followed by a 7 day taper.

AzithromycinDRUG

Azithromycin 250 mg PO daily for 2 weeks, then 3 times per week until 3 months

MontelukastDRUG

Montelukast 10 mg PO qhs for 3 months

SymbicortDRUG

Symbicort 200/6 mcg, 2 inhalations every 12 hours for 3 months

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Cumulative incidence of new chronic lung disease

The incidence rate of new non-infectious pulmonary complications within the 6 month follow-up period will be calculated. Non-infectious pulmonary complications include new airflow obstruction, new restrictive lung disease, and new mixed obstruction/restriction as measured by spirometry at study enrolment, 2 and 8 weeks following viral infection, and by full pulmonary function tests at 3 and 6 weeks following viral infection.

Time frame: 6 months following diagnosis of the viral respiratory tract infection

Secondary Outcomes

Prevalence of non-infectious pulmonary complications

Non-infectious pulmonary complications (NIPCs) include airflow obstruction, restrictive lung disease, and mixed obstruction/restriction as determined by pulmonary function tests. The prevalence of NIPCs will be determined among subjects surviving to 6 months post viral respiratory tract infection.

Time frame: 6 months following the diagnosis of viral respiratory tract infection

Long-term functional impairment as defined by need for supplemental oxygen

The percentage of subjects needing at least 1 month of supplemental oxygen on most days per week, not counting the period of symptomatic viral respiratory tract infection, will be determined in both arms.

Time frame: 6 months post viral respiratory tract infection

Patient-perceived long-term functional impairment

A FACT-BMT questionnaire will be administered at baseline and again to subjects surviving 6 months post respiratory tract infection to measure patient-perceived functional impairment.

Time frame: 6 months post viral respiratory tract infection

Time to clearance of viral infection

Subjects in whom a respiratory virus is detected will undergo repeat testing every 2 weeks until the virus is no longer detectable. This is an exploratory analysis. The natural history of many of these community-acquired viruses in the transplant population is not known.

Time frame: Every 2 weeks until virus is no longer detectable

Incidence of progression to respiratory failure

This endpoint includes admission to hospital because of documented desaturation, need for supplemental oxygen, and need for mechanical ventilation.

Time frame: 21 days after enrolment

Incidence of bacterial or fungal superinfection

The incidence of secondary bacterial and fungal pneumonias will be compared in the two arms, to verify that the added immunosuppression does not contribute to further infectious complications.

Time frame: Within 21 days after enrolment

Incidence of various other infectious complications

The incidence of various other infectious complications, specifically including but not limited to CMV reactivations and CMV disease, zoster, and septicemia will be monitored in both arms.

Time frame: Within 6 months after enrolment

Overall survival from date of viral respiratory tract infection

Time frame: 3 months post enrolment

Overall survival from date of viral respiratory tract infection

Time frame: 6 months post enrolment

Overall survival from date of transplant to end of study follow-up

Time frame: 6 months post enrolment

Overall survival at 1 year post-transplant

This measure will be applied to the group overall and also analyzed according to subgroups of patients presenting viral respiratory tract infections within 30 days of transplant, 31-100 days of transplant, and 101-365 days of transplant.

Time frame: 1 year post-transplant

Cumulative incidence of death attributable to transplant associated lung disease

Time frame: 6 months post enrolment

Cumulative incidence of death from other causes

Time frame: 6 months post enrolment

Steroids, Azithromycin, Montelukast, and Symbicort (SAMS) for Viral Respiratory Tract Infection Post Allotransplant

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes