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

NCT01432080 | Terminated Phase 2

• 1 other identifier: HMR1102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months following diagnosis of the viral respiratory tract infection

Secondary Outcomes (13)

• Prevalence of non-infectious pulmonary complications

  6 months following the diagnosis of viral respiratory tract infection

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

  6 months post viral respiratory tract infection

• Patient-perceived long-term functional impairment

  6 months post viral respiratory tract infection

• Time to clearance of viral infection

  Every 2 weeks until virus is no longer detectable

• Incidence of progression to respiratory failure

  21 days after enrolment

Study Arms (2)

Standard of Care

NO INTERVENTION

Standard of Care includes fluids, antipyretics, ribavirin for RSV infection, and oseltamivir for influenza infection, and intravenous immune globulin for patients with low IgG levels.

SAMS

EXPERIMENTAL

Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).

Drug: Prednisone; Drug: Azithromycin; Drug: Montelukast; Drug: Symbicort

Interventions

Prednisone DRUG

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

Also known as: Deltasone, Steroids

SAMS

Azithromycin DRUG

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

SAMS

Montelukast DRUG

Montelukast 10 mg PO qhs for 3 months

Also known as: Singulair

SAMS

Symbicort DRUG

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

Also known as: Budesonide, Formoterol

SAMS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead
• The Canadian Blood and Marrow Transplant Group: collaborator

Study Sites (1)

Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont)

Montreal, Quebec, H1T 2M4, Canada

Location

Related Links

• Maisonneuve-Rosemont Hospital's Stem Cell Transplant Program

MeSH Terms

Conditions

Respiratory Tract Infections; Bronchiolitis Obliterans; Cryptogenic Organizing Pneumonia; Lung Diseases, Interstitial; Pulmonary Disease, Chronic Obstructive

Interventions

Prednisone; Steroids; Azithromycin; montelukast; Budesonide, Formoterol Fumarate Drug Combination; Budesonide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases; Bronchiolitis; Bronchitis; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Organizing Pneumonia; Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Ethanolamines; Amino Alcohols; Alcohols; Amines; Pregnenediones; Pregnenes; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Elizabeth F Krakow, MD,CM, FRCPC

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

• Sandra Cohen, MD, FRCPC

  Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow in Hematopoietic Cell Transplantation

Study Record Dates

• First Submitted: September 8, 2011
• First Posted: September 12, 2011
• Study Start: September 1, 2011
• Primary Completion: December 1, 2012
• Study Completion: December 30, 2013
• Last Updated: October 20, 2021

Record last verified: 2021-10

Locations

CA (1)