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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by Maisonneuve-Rosemont Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
The Canadian Blood and Marrow Transplant Group
Information provided by (Responsible Party):
Elizabeth Krakow, Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier:
NCT01432080
First received: September 8, 2011
Last updated: January 8, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Respiratory Tract Infections
Bronchiolitis Obliterans
Cryptogenic Organizing Pneumonia
Lung Diseases, Interstitial
Drug: Prednisone
Drug: Azithromycin
Drug: Montelukast
Drug: Symbicort
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Does Increasing Immunosuppression Prevent Transplant-associated Lung-disease Triggered by Viral Respiratory Tract Infection Following Allogeneic Stem Cell Transplant? A Pilot Study

Resource links provided by NLM:


Further study details as provided by Maisonneuve-Rosemont Hospital:

Primary Outcome Measures:
  • Cumulative incidence of new chronic lung disease [ Time Frame: 6 months following diagnosis of the viral respiratory tract infection ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Prevalence of non-infectious pulmonary complications [ Time Frame: 6 months following the diagnosis of viral respiratory tract infection ] [ Designated as safety issue: No ]
    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.

  • Long-term functional impairment as defined by need for supplemental oxygen [ Time Frame: 6 months post viral respiratory tract infection ] [ Designated as safety issue: No ]
    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.

  • Patient-perceived long-term functional impairment [ Time Frame: 6 months post viral respiratory tract infection ] [ Designated as safety issue: No ]
    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 to clearance of viral infection [ Time Frame: Every 2 weeks until virus is no longer detectable ] [ Designated as safety issue: No ]
    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.

  • Incidence of progression to respiratory failure [ Time Frame: 21 days after enrolment ] [ Designated as safety issue: Yes ]
    This endpoint includes admission to hospital because of documented desaturation, need for supplemental oxygen, and need for mechanical ventilation.

  • Incidence of bacterial or fungal superinfection [ Time Frame: Within 21 days after enrolment ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of various other infectious complications [ Time Frame: Within 6 months after enrolment ] [ Designated as safety issue: Yes ]
    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.

  • Overall survival from date of viral respiratory tract infection [ Time Frame: 3 months post enrolment ] [ Designated as safety issue: No ]
  • Overall survival from date of viral respiratory tract infection [ Time Frame: 6 months post enrolment ] [ Designated as safety issue: No ]
  • Overall survival from date of transplant to end of study follow-up [ Time Frame: 6 months post enrolment ] [ Designated as safety issue: No ]
  • Overall survival at 1 year post-transplant [ Time Frame: 1 year post-transplant ] [ Designated as safety issue: No ]
    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.

  • Cumulative incidence of death attributable to transplant associated lung disease [ Time Frame: 6 months post enrolment ] [ Designated as safety issue: No ]
  • Cumulative incidence of death from other causes [ Time Frame: 6 months post enrolment ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: September 2011
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Standard of Care
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.
Experimental: SAMS
Subjects randomized to the SAMS arm will receive a four-drug combination (Steroids, Azithromycin, Montelukast, and Symbicort).
Drug: Prednisone
Prednisone 0.75 mg/kg actual body weight/day PO for 7 days followed by a 7 day taper.
Other Names:
  • Deltasone
  • Steroids
Drug: Azithromycin
Azithromycin 250 mg PO daily for 2 weeks, then 3 times per week until 3 months
Drug: Montelukast
Montelukast 10 mg PO qhs for 3 months
Other Name: Singulair
Drug: Symbicort
Symbicort 200/6 mcg, 2 inhalations every 12 hours for 3 months
Other Names:
  • Budesonide
  • Formoterol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01432080

Contacts
Contact: Johanne Blais (514) 252-3400 ext 3295 johanne_blais.hmr@ssss.gouv.qc.ca

Locations
Canada, Quebec
Maisonneuve-Rosemont Hospital (Hôpital Maisonneuve-Rosemont) Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Johanne Blais    (514) 252-3400 ext 3295    johanne_blais.hmr@ssss.gouv.qc.ca   
Contact: Sandra Cohen, MD, FRCPC    (514) 252-3404    sandra.cohen@umontreal.ca   
Principal Investigator: Elizabeth F Krakow, MD,CM, FRCPC         
Principal Investigator: Sandra Cohen, MD, FRCPC         
Sponsors and Collaborators
Maisonneuve-Rosemont Hospital
The Canadian Blood and Marrow Transplant Group
Investigators
Principal Investigator: Elizabeth F Krakow, MD,CM, FRCPC Maisonneuve-Rosemont Hospital
Principal Investigator: Sandra Cohen, MD, FRCPC Maisonneuve-Rosemont Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Elizabeth Krakow, Fellow in Hematopoietic Cell Transplantation, Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier: NCT01432080     History of Changes
Other Study ID Numbers: HMR1102
Study First Received: September 8, 2011
Last Updated: January 8, 2012
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by Maisonneuve-Rosemont Hospital:
Pulmonary disease, chronic obstructive
Viral respiratory tract infections
Respiratory syncytial viruses
Influenza virus A
Influenza virus B
Transplantation, Allogeneic

Additional relevant MeSH terms:
Lung Diseases, Interstitial
Bronchiolitis
Bronchiolitis Obliterans
Lung Diseases
Pneumonia
Respiratory Tract Infections
Cryptogenic Organizing Pneumonia
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Infection
Idiopathic Interstitial Pneumonias
Prednisone
Montelukast
Azithromycin
Symbicort
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leukotriene Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on July 29, 2014