Early Detection and Management of Bronchiolitis Obliterans Syndrome Following Pediatric Hematopoietic Stem Cell Transplantation

NCT03072849 | Completed DMC

• 1 other identifier: SCT 1214 BOS
• Study Type: observational
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine whether or not early spirometric detection and management of obstructive lung disease with combined fluticasone/azithromycin/montelukast therapy (FAM) can attenuate declining lung function, prevent the development of bronchiolitis obliterans, and improve patient outcomes following hematopoietic stem cell transplant.

Conditions

Bronchiolitis Obliterans Syndrome

Keywords

Pediatrics; Airflow obstruction; Chronic graft-vs-host disease; Bronchiolitis obliterans syndrome

Outcome Measures

Primary Outcomes (2)

• Lung function

  Change in lung function at 12 and 24 months post-HSCT

  2 years

• Survival

  Overall survival at 2 years post-HSCT

  2-4 years

Secondary Outcomes (1)

• Risk factor assessment

  2 years

Study Arms (1)

Stem Cell Transplant Recipients

Pediatric patients ages 6-18 years who have received allogenic hematopoietic stem cell transplant for any reason.

Procedure: Pulmonary function testing; Drug: FAM Therapy

Interventions

Pulmonary function testing PROCEDURE

Each enrolled patient will receive pulmonary function testing every three months. Pulmonary function testing includes spirometry, plethysmography, and diffusion capacity measurements.

Also known as: PFT, Spirometry, Plethysmography, Diffusion capacity

Stem Cell Transplant Recipients

FAM Therapy DRUG

All patients who have evidence of early airflow obstruction on pulmonary function testing will be started on FAM therapy. Early airflow obstruction is defined by a FEV1 decline of ≥10% predicted in addition to a FVC \<0.8.

Also known as: Fluticasone (Inhaled), Azithromycin, Montelukast

Stem Cell Transplant Recipients

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients undergoing allogenic hematopoietic stem cell transplant

You may qualify if:

• Diagnosis: Patients undergoing myeloablative allogenic hematopoietic stem cell transplant for any indication (both malignant and non-malignant) are eligible.
• Graft: Eligible patients will have one or more of the following donor stem cell sources:
• Bone marrow
• Placental blood (umbilical cord blood)
• Cytokine mobilized peripheral blood
• Eligible patients will have one of the following sources of donor stem cells:
• HLA matched family member
• Partially matched family member (mismatched for a single HLA locus at A, B, C or DR)
• Fully HLA matched or partially mismatched unrelated marrow or peripheral blood stem cells (per institutional donor selection standards)
• HLA matched or partially mismatched (at least 4/6 match at A, B, DR) cord blood.
• Conditioning Regimen: Patients expecting to receive any type of myeloablative HSCT conditioning regimen are eligible.
• Prior therapies: Patients undergoing stem cell transplant of any kind.
• Required laboratory parameters: Patients able to adequately perform pulmonary function testing per ATS/ERS guidelines, as determined by the enrolling investigator and trained respiratory therapists.
• The patient and/or the patient's legally authorized guardian must acknowledge in writing that consent to become a study subject has been obtained in accordance with the institutional policies approved by the U.S. Department of Health and Human Services. Informed consent must be signed prior to registration on study.

You may not qualify if:

• Subjects with a previous solid organ transplant.
• Recurrent or progressive malignancy requiring anti-cancer therapy.
• Subjects with evidence of underlying obstructive pulmonary disease prior to transplant (clinical history of asthma or baseline FEV1 \<80% predicted with FEV1/FVC \<80%).
• Known history of allergy or intolerance to Montelukast, Zafirleukast, Azithromycin, Erythromycin, Clarithromycin, Prednisone, or Sirolimus.
• Chronic supplemental oxygen requirement or hypoxemia \<92% SpO2.
• Clinical asthma (variable and recurrent symptoms of airflow obstruction and airway hyper-responsiveness).
• Pregnancy or nursing: All females of childbearing age must have a negative serum or urine pregnancy test \<7 days before study drug administration.
• Chronic treatment with any inhaled steroid for \>1 month in past three months.
• Treatment with montelukast or zafirukast for \>1 month in past three months.
• Treatment with systemic steroids for \>1 month in past three months.
• Treatment with any FDA non-approved study medication within the past four weeks. Off label treatment with FDA approved medication is allowed.
• Evidence of any viral, bacterial, or fungal infection involving the lung and not responding to appropriate treatment.
• Inability to perform pulmonary function testing (PFT), as determined by the enrolling investigator or PFT lab.
• Any condition that, in the opinion of the enrolling investigator, would interfere with the subject's ability to comply with the study requirements.

Sponsors & Collaborators

• Ann & Robert H Lurie Children's Hospital of Chicago: lead

Study Sites (1)

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Related Publications (11)

• Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG, Clark JG. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2003 Jul 15;168(2):208-14. doi: 10.1164/rccm.200212-1468OC. Epub 2003 Mar 20.

  PMID: 12649126 BACKGROUND

• Bergeron A, Belle A, Chevret S, Ribaud P, Devergie A, Esperou H, Ades L, Gluckman E, Socie G, Tazi A. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007 May;39(9):547-53. doi: 10.1038/sj.bmt.1705637. Epub 2007 Mar 12.

  PMID: 17351647 BACKGROUND

• Bashoura L, Gupta S, Jain A, Couriel DR, Komanduri KV, Eapen GA, Safdar A, Broglio KR, Adachi R, Dickey BF. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008 Jan;41(1):63-7. doi: 10.1038/sj.bmt.1705877. Epub 2007 Oct 15.

  PMID: 17934530 BACKGROUND

• Kaya Z, Weiner DJ, Yilmaz D, Rowan J, Goyal RK. Lung function, pulmonary complications, and mortality after allogeneic blood and marrow transplantation in children. Biol Blood Marrow Transplant. 2009 Jul;15(7):817-26. doi: 10.1016/j.bbmt.2009.03.019.

  PMID: 19539213 BACKGROUND

• Norman BC, Jacobsohn DA, Williams KM, Au BK, Au MA, Lee SJ, Moravec CK, Chien JW. Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: a case series of eight patients. Bone Marrow Transplant. 2011 Oct;46(10):1369-73. doi: 10.1038/bmt.2010.311. Epub 2010 Dec 6.

  PMID: 21132024 BACKGROUND

• Hildebrandt GC, Fazekas T, Lawitschka A, Bertz H, Greinix H, Halter J, Pavletic SZ, Holler E, Wolff D. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant. 2011 Oct;46(10):1283-95. doi: 10.1038/bmt.2011.35. Epub 2011 Mar 28.

  PMID: 21441964 BACKGROUND

• Pulsipher MA, Skinner R, McDonald GB, Hingorani S, Armenian SH, Cooke KR, Gracia C, Petryk A, Bhatia S, Bunin N, Nieder ML, Dvorak CC, Sung L, Sanders JE, Kurtzberg J, Baker KS. National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines. Biol Blood Marrow Transplant. 2012 Mar;18(3):334-47. doi: 10.1016/j.bbmt.2012.01.003. Epub 2012 Jan 14.

  PMID: 22248713 BACKGROUND

• Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C, Burns LJ, Chaudhri N, Davies S, Okamoto S, Seber A, Socie G, Szer J, Van Lint MT, Wingard JR, Tichelli A; Center for International Blood and Marrow Transplant Research; American Society for Blood and Marrow Transplantation; European Group for Blood and Marrow Transplantation; Asia-Pacific Blood and Marrow Transplantation Group; Bone Marrow Transplant Society of Australia and New Zealand; East Mediterranean Blood and Marrow Transplantation Group; Sociedade Brasileira de Transplante de Medula Ossea. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Bone Marrow Transplant. 2012 Mar;47(3):337-41. doi: 10.1038/bmt.2012.5.

  PMID: 22395764 BACKGROUND

• Gassas A, Craig-Barnes H, Dell S, Doyle J, Schechter T, Sung L, Egeler M, Palaniyar N. Chest health surveillance utility in the early detection of bronchiolitis obliterans syndrome in children after allo-SCT. Bone Marrow Transplant. 2013 Jun;48(6):814-8. doi: 10.1038/bmt.2012.228. Epub 2012 Nov 19.

  PMID: 23165500 BACKGROUND

• Prais D, Sinik MM, Stein J, Mei-Zahav M, Mussaffi H, Steuer G, Hananya S, Krauss A, Yaniv I, Blau H. Effectiveness of long-term routine pulmonary function surveillance following pediatric hematopoietic stem cell transplantation. Pediatr Pulmonol. 2014 Nov;49(11):1124-32. doi: 10.1002/ppul.22944. Epub 2013 Nov 4.

  PMID: 24574432 BACKGROUND

• Madanat-Harjuoja LM, Valjento S, Vettenranta K, Kajosaari M, Dyba T, Taskinen M. Pulmonary function following allogeneic stem cell transplantation in childhood: a retrospective cohort study of 51 patients. Pediatr Transplant. 2014 Sep;18(6):617-24. doi: 10.1111/petr.12313. Epub 2014 Jul 7.

  PMID: 25041660 BACKGROUND

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Respiratory Physiological Phenomena; Fluticasone; Inhalation; Azithromycin; montelukast

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Circulatory and Respiratory Physiological Phenomena; Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Respiratory Mechanics; Respiration; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MS

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 7, 2017
• Study Start: April 1, 2015
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: November 19, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)