Complement and Graft-versus-host Disease

NCT01520623 | Completed DMC

• 1 other identifier: CRC 08025
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 3

Brief Summary

Allogeneic haematopoietic stem cell transplantation (HSCT) often remains the only curative treatment for haematological malignancies. The anti-leukaemic effect of allogeneic HSCT, called the GvL (Graf-versus-Leukemia) effect, is often associated to the development of an immune response against healthy recipient cells leading to a graft-versus-host disease (GvHD) in 20 to 70% of allogeneic HSCT. Acute GvHD, that usually targets the skin, the gastrointestinal (GI) tract and the liver, is an important cause of morbidity and mortality after allogeneic HSCT, particularly in the case of GI GvHD. The main goal of the research in the field of allogeneic HSCT is to determine strategies that could decrease the risk of GvHD without affecting the GvL effect. According to GVHD experimental models, it is likely that GvL but not GvHD may occur in the absence of inflammatory signals induced by the transplant-associated conditioning. Based on this hypothesis, we have chosen to analyse the role of Complement system in patients who received allogeneic HSCT. Indeed, Complement system is a major actor of inflammation and in the generation of tissue destruction, both of which are involved in the physiopathology of GVHD. Furthermore, it might be a potential target of some available inhibitory drugs (purified C1-Inhibitor, anti-C5 antibodies) in a preventive or curative manner in such patients. Preliminary data obtained from 34 allografted patients in our institution suggest that Complement activation by the classical pathway is correlated to the occurrence of GI GVHD. The goal of our current project, in order to confirm these preliminary results in a larger series, is to explore Complement system activation in patients who received allogeneic HSCT in three Adult Hematology departments in Paris fot two years and to correlate the biological results to the clinical events occurring after HSCT.

Conditions

Allografted With Myeloablative Conditioning

Keywords

Allogeneic haematopoietic stem cell transplantation (HSCT); Myeloablative conditioning for an haematological malignancy; Graft-versus-host disease (GvHD); Activation of complement system; Gut GVHD

Outcome Measures

Primary Outcomes (1)

• Activation of the complement system and the development of acute gut GvHD

  Assessment of the activation of the complement system after human allogeneic stem cell transplantation and of its potential correlation with the development of acute gut GvHD

  12 weeks

Secondary Outcomes (2)

• Overall survival

  2 years

• Overall survival without relapse

  2 Years

Study Arms (1)

Allografted patients

OTHER

Allografted patients with myeloablative conditioning for an haematological malignancy. Patients will be followed for at least 12 months after transplantation and blood samples drawn before conditioning and once a week for 12 weeks after transplantation to analyze the serum concentration of Complement factors (C3, C4, B factor), Complement regulatory proteins (C1-inhibitor, I and H Factors) and analysis of the surface expression of Complement regulatory molecules such as CD46, CD55 and CD59 and the serum inflammatory cytokine levels

Other: Serum concentration /Serum inflammatory

Interventions

Serum concentration /Serum inflammatory OTHER

Allografted patients with myeloablative conditioning for an haematological malignancy. Patients will be followed for at least 12 months after transplantation and blood samples drawn before conditioning and once a week for 12 weeks after transplantation to analyze the serum concentration of Complement factors (C3, C4, B factor), Complement regulatory proteins (C1-inhibitor, I and H Factors) and analysis of the surface expression of Complement regulatory molecules such as CD46, CD55 and CD59 and the serum inflammatory cytokine levels

Allografted patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Allografted patients with myeloablative conditioning for an haematological malignancy
• Age \> 18 years old and \< 65 years.
• The patient must have access to social insurance according to local regulations.
• Patient must give a written informed consent (personally signed and dated) before completing any study related procedure

You may not qualify if:

• Age \< 18 years old and \> 65 years
• Patient with active infection HIV, HTLV1, Hepatite B ou C
• Uncontrolled infection(s), (i.e. documented bacterial, parasitical, or fungal infection).
• Patient with lupus
• Patient with transaminases \> 5N, TP\<30% with Facteur V \< 30% before allogreffe
• Creatinine clearance \< 50ml/min
• Absence of any psychological condition potentially hampering signing informed consent
• Patient refused to sign informed consent

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Clinical haematology and BMT unit,Necker Hospital, Paris: collaborator
• Clinical haematology and BMT unit,Saint Antoine Hospital, Paris: collaborator
• Clinical haematology and BMT unit,Saint Louis Hospital,Paris: collaborator
• European Georges Pompidou Hospital: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (3)

Saint Louis Hospital

Paris, 75010, France

Location

Saint Antoine Hospital

Paris, 75012, France

Location

Necker Hospital

Paris, 75, France

Location

Related Publications (2)

• Rubio MT, Bouillie M, Bouazza N, Coman T, Trebeden-Negre H, Gomez A, Suarez F, Sibon D, Brignier A, Paubelle E, Nguyen-Khoc S, Cavazzana M, Lantz O, Mohty M, Urien S, Hermine O. Pre-transplant donor CD4- invariant NKT cell expansion capacity predicts the occurrence of acute graft-versus-host disease. Leukemia. 2017 Apr;31(4):903-912. doi: 10.1038/leu.2016.281. Epub 2016 Oct 14.

  PMID: 27740636 RESULT

• Notarantonio AB, D'aveni-Piney M, Pagliuca S, Ashraf Y, Galimard JE, Xhaard A, Marcais A, Suarez F, Brissot E, Feugier P, Urien S, Bouazza N, Jacquelin S, Meatchi T, Bruneval P, Fremeaux-Bacchi V, Peffault De Latour R, Hermine O, Durey-Dragon MA, Rubio MT. Systemic complement activation influences outcomes after allogeneic hematopoietic cell transplantation: A prospective French multicenter trial. Am J Hematol. 2023 Oct;98(10):1559-1570. doi: 10.1002/ajh.27030. Epub 2023 Jul 22.

  PMID: 37483161 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Marie-Thérèse RUBIO, MD, PhD

  Saint Antoine Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2011
• First Posted: January 30, 2012
• Study Start: April 1, 2010
• Primary Completion: February 1, 2013
• Study Completion: July 1, 2013
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

FR (3)