Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

Malignant Hematological Diseases Clinical Trial

— ALLOZITHRO  

Official title:

Evaluation of the Efficacy of Azithromycin to Prevent Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01959100
• Other study ID #: P120110
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 2014
• Est. completion date: August 2022

Study information

• Verified date: December 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 480
• Est. completion date: August 2022
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bronchiolitis
• Bronchiolitis Obliterans
• Hematologic Diseases
• Malignant Hematological Diseases

Intervention

Drug:
• Azithromycin
250 mg x 3/week per os during a meal for a period of 2 years
• Placebo
250 mg x 3/week during a meal for a period of 2 years

Locations

Country	Name	City	State
France	Saint Louis	Paris	Ile De France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

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, Socié G, Tazi A. Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Airflow decline (AFD)-free survival	Defined on the criteria from Chien JW et al (Am J Resp Crit Care Med 2003;168:208-14) by an annualized decline of percent predicted forced expiratory volume in 1 second (FEV1) of more than 5%	2 year after allogeneic HSCT
Secondary	Overall survival		within 2 years of inclusion
Secondary	Occurrence of late-onset pulmonary non-infectious complications (=bronchiolitis obliterans syndrome, SBO)	bronchiolitis obliterans syndrome (SBO) is defined as the absence of infection with an forced expiratory volume in 1 second (FEV1) of <75% of predicted or a decline of > 10% and FEV1/Slow vital capacity (SVC) < 0.7 or residual volume (RV) or RV/total lung capacity (TLC) > 120%, and interstitial lung disease, which is defined as the onset of new interstitial lung abnormalities observed with a lung CT scan and the absence of infection.	within 2 years after inclusion
Secondary	Variation of pulmonary function testing parameters	variation in mean forced expiratory volume in 1 second (FEV1) decline, forced vital capacity (FVC), residual volume (RV), Total Lung capacity (TLC), Forced expiratory flow at 25% point to the 75% point of Forced Vital Capacity (FEF25-75%) as compared to baseline values (at inclusion)	within 2 years after inclusion
Secondary	Occurrence of acute and chronic extra-thoracic graft versus host disease (GVHD)		within 2 years after inclusion
Secondary	Cumulative incidence of hematological relapse		within the 2 years after inclusion
Secondary	Quality of life		within 2 years after inclusion
Secondary	Tolerance	adverse events	within 2 years of inclusion
Secondary	Cumulative dose of steroids treatment		within the 2 years after inclusion