Biomarkers for Acute Graft-versus-host Disease

• Conditions: Acute GVH Disease
• Interventions: Other: no intervention

• Registration Number: NCT02254798
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Validation of already described biomarkers on acute GVHD prediction and severity Fecal calprotectin and alpha 1 anti-trypsin, plasmatic RER3a, IL-8, Elafin, TNFaR1, IL-2R alpha, HGF

Detailed Description

Description of the project: The main objective of this prospective biological single center study (non interventional) is to identify non invasive biomarkers able to diagnose acute GVHD and/or predict outcome of patients with acute GVHD. The primary objective of the study is double: (1): to evaluate markers as diagnostic markers of GVHD (2): to evaluate the potential of the markers as risk factor for steroid-refractory acute GVHD occurrence. Secondary objectives are: -to evaluate the markers as risk factors for GVHD -to evaluate the potential of these markers as prognostic factors of 6-month non-relapse mortality in patients with acute GVHD-to evaluate the additional value of the biomarkers to predict GVHD or steroid-refractory GVHD as compared to other known and routinely used risk factors (clinical grading system, performance status, albuminemia...). Stools and blood will be on day 7, 14, 21, 28 after transplantation and the first day of digestive GVHD. Management of patients will not differ from the usual care. Fecal calprotectin and alpha 1 anti-trypsin, plasmatic RER3a, IL-8, Elafin, TNFaR1, IL-2R alpha, HGF will be measured at each points by ELISA tests. 315 patients would be sufficient to estimate the area under the ROC curve with a half-width of the 99% confidence interval of 0.05, assuming 60% of patients would develop acute GVHD, and normally distributed markers. The diagnosis and prognosis values will be analyzed separately.

Expected results: If some biomarkers are found significantly associated with diagnosis or prognosis of acute GVHD, they will be compared with the current clinical, biological and histological markers. Indeed, these markers have a clinical potential impact only if they give similar or better information than routine currently available markers, ie: clinical GVHD grading system, performance status, gut endoscopy and histology. The non-invasivity of these biomarkers should also be taken into account (in comparison to histology).

Identification of diagnostic markers will avoid useless treatment with high dose corticosteroids in patients without GVHD Identification of prognostic markers will comfort the decision of a second-line treatment sooner than usually, ie: at GVHD onset. Indeed, the onset of a second-line treatment after a steroid-refractory GVHD varies from 3 to 21 days depending on clinical evolution of patients. If some prognostic markers are available at diagnosis, delay in second-line treatment can be shortened and the patient can consequently have an increased chance to response to an early treatment.

Identification of prognostic markers will also guide the corticosteroids decrease in patients with good prognosis GVHD

Study Timeline

• Study Start: 2014-01
• Status Verified: 2014-09
• Study First Submitted: 2014-09-17
• Study First Submitted QC: 2014-09-29
• Last Update Submitted: 2014-09-29
• Study First Posted: 2014-10-02
• Last Update Posted: 2014-10-02
• Primary Completion: 2017-06
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 315

Inclusion Criteria

• adult patients receiving an allogeneic transplant
• informed consent signed

Exclusion Criteria

• patient refusal

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Transplanted patients	no intervention	No intervention Prospective registration of patients receiving an allogeneic hematopoietic stem cell transplant

Primary Outcome Measures

Name	Time	Method
Number of patients with an Acute Graft-versus-Host disease	The 6 first months after transplantation	Evaluation of fecal and plasmatic markers as diagnostic markers of GVHD
Number of patients with an Acute Graft-versus-Host disease refractory to steroids	14 days after acute graft-versus-host disease	to evaluate the potential of these markers as risk factors for steroid-refractory acute GVHD occurrence

Trial Locations

Locations (1)

Hôpital Saint-Louis; 🇫🇷 Paris, France