Clinical trial NCT01959100: Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Malignant Hematological Diseases
Keywords: hematopoietic stem cell transplantation
pulmonary non-infectious complications
bronchiolitis obliterans syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2013-10-09
Enrollment: 480
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The occurrence of bronchiolitis obliterans syndrome (SBO) after allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be a chronic pulmonary graft versus host disease (GVHD) that is associated with significant mortality and morbidity. The reported incidence of SBO varies from 6 to 26% of allogeneic HSC recipients and is usually diagnosed within 2 years after transplantation. The diagnosis of SBO relies on the occurrence of a new airflow obstruction identified during pulmonary function testing, and the definition differs between studies. Currently, no curative immunosuppressive treatment is available, and recent data suggest that the use of these treatments, especially corticosteroids, should be limited because of their toxicity. The impairment of lung function parameters is likely caused by fibrous small airway lesions. Few data on the pathogenesis of SBO after allogeneic HSCT are available. Several hypotheses are based on the occurrence of SBO during chronic graft rejection after lung transplantation, which shares many clinical and histopathological similarities with SBO after allogeneic HSCT. One hypothesis is that the first step leading to SBO is lung epithelium injury. SBO is then identified as an alloimmune reaction with only one clearly identified risk factor: extrathoracic chronic GVHD. Due to their anti-inflammatory and immunomodulatory properties, recent data suggest that low-dose macrolides may be effective at preventing SBO after lung transplants. This well-tolerated treatment may be useful for preventing SBO after allogeneic HSCT.

The objective of this Phase 3 multicentre randomized, double-blinded, clinical trial is to evaluate the efficacy of azithromycin in preventing BO syndrome after allogeneic HSCT in patients with malignant hematological diseases.


Eligibility criteria: Inclusion Criteria:

* Patients\> 16 years old
* Experimenting an allogeneic HSCT for a hematologic malignancy
* Pre-transplantation Pulmonary Function Testing
* With written informed consent

Exclusion Criteria:

* Allergy or Intolerance to azithromycin, macrolides or ketolide or excipient
* Prolonged corrected QT (QTc) interval (\>450 msec)
* Taking medications that prolong the QTc interval (Cisapride, ergotamine, dyhydroergotamine)
* Taking ergotamine and dyhydroergotamine due to the risk of ergotism
* Family history of a prolonged QTc interval.
* History of congestive heart failure
* Taking colchicine Severe liver insufficiency • History of infection due to atypical mycobacteria

Primary outcomes:
measure: Airflow decline (AFD)-free survival
timeFrame: 2 year after allogeneic HSCT
Secondary outcomes:
measure: Overall survival
timeFrame: within 2 years of inclusion
measure: Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO)
timeFrame: within 2 years after inclusion
measure: Variation of pulmonary function testing parameters
timeFrame: within 2 years after inclusion
measure: Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD)
timeFrame: within 2 years after inclusion
measure: Cumulative incidence of hematological relapse
timeFrame: within the 2 years after inclusion
measure: Quality of life
timeFrame: within 2 years after inclusion
measure: Tolerance
timeFrame: within 2 years of inclusion
measure: Cumulative dose of steroids treatment
timeFrame: within the 2 years after inclusion
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis
state: Ile De France
Study officials:
References:
citation: Bergeron A, Chevret S, Chagnon K, Godet C, Bergot E, Peffault de Latour R, Dominique S, de Revel T, Juvin K, Maillard N, Reman O, Contentin N, Robin M, Buzyn A, Socie G, Tazi A. Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2015 Jun 1;191(11):1242-9. doi: 10.1164/rccm.201410-1818OC.
citation: Bergeron A, Chevret S, Granata A, Chevallier P, Vincent L, Huynh A, Tabrizi R, Labussiere-Wallet H, Bernard M, Chantepie S, Bay JO, Thiebaut-Bertrand A, Thepot S, Contentin N, Fornecker LM, Maillard N, Risso K, Berceanu A, Blaise D, Peffault de La Tour R, Chien JW, Coiteux V, Socie G; ALLOZITHRO Study Investigators. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):557-566. doi: 10.1001/jama.2017.9938.