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Trial record 27 of 1165 for:    Recruiting, Not yet recruiting, Available Studies | "Arthritis"

Relationship Between T LYmphocytes Depletion and Clinical Response to RITUXimab in Rheumatoid Arthritis (LYRITUX) (LYRITUX)

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ClinicalTrials.gov Identifier: NCT02304354
Recruitment Status : Recruiting
First Posted : December 1, 2014
Last Update Posted : October 26, 2017
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours

Brief Summary:

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24.

In a recent retrospective study, a CD4+ T-lymphocytes depletion was observed after a first course of rituximab in RA patients. The absolute CD4+ number at week 12 was 37% (±33) of the baseline value, leading to < 200 cells/µL in 5% of patients. Interestingly the absence of CD4+ T-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of T-lymphocytes in the mechanism of action of rituximab. So far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular T-lymphocytes, to monitor rituximab-treated RA patients.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Rituximab Phase 3

Detailed Description:

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, (Edwards, Szczepanski et al. 2004; Cohen, Emery et al. 2006; Emery, Fleischmann et al. 2006) 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. In the pathogenesis of RA, B and T lymphocytes are tightly linked through the APC fonction and cytokines production of B lymphocytes. At present, a white blood cells count is recommended in routine every 3 months in patients receiving rituximab, since cases of neutropenia have been observed in approximately 8% of patients with lymphoma after treatment. In RA patients, B lymphocytes count before each rituximab course should be done to prevent opportunistic infections (Pham, Fautrel et al. 2008).

In a recent retrospective study, a CD4+ T-lymphocytes depletion was observed after a first course of rituximab in RA patients. The absolute CD4+ number at week 12 was 37% (±33) of the baseline value, leading to < 200 cells/µL in 5% of patients. Interestingly the absence of CD4+ T-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of T-lymphocytes in the mechanism of action of rituximab (Mélet, Mulleman et al. 2013). Moreover, few case reports of RA patients developing opportunist infections in conjunction with CD4+ T-lymphocyte depletion have been published (Teichmann, Woenckhaus et al. 2008; Clifford, Ances et al. 2011). So far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular T-lymphocytes, to monitor rituximab-treated RA patients.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Relationship Between T LYmphocytes Depletion and Clinical Response to RITUXimab in Rheumatoid Arthritis (LYRITUX)
Actual Study Start Date : March 9, 2015
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: Rituximab
two intravenous infusions of 1000 mg with a two-week interval between them
Drug: Rituximab
For rheumatoid arthritis, MabThera is given as two intravenous infusions of 1000 mg with a two-week interval between them. Patients usually respond to treatment within 16 to 24 weeks of initial treatment. After 24 weeks, treatment can be repeated depending on the patient's response.
Other Name: MabThera




Primary Outcome Measures :
  1. DAS28 [ Time Frame: up week 48 ]
    Disease Activity Score on 28 joints (DAS28) is a composite score that comprise tender joints count, swollen joints count, patient's disease activity on visual analog scale and erythrocyte sedimentation rate. DAS28 will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

  2. T-lymphocyte count [ Time Frame: up to week 48 ]
    T-lymphocyte count will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).


Secondary Outcome Measures :
  1. C reactive Protein (CRP) [ Time Frame: Baseline up to 48 weeks ]
    CRP will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

  2. Immunoglobulines G [ Time Frame: Baseline up to 48 weeks ]
    Immunoglobuline G concentrations will be measured at baseline, week 16 and at the end of the study (i.e. between week 24 and week 48).

  3. Cytokine profile [ Time Frame: Baseline up to 48 weeks ]
    the following cytokines (APRIL, BAFF, TNF, IL-1 alpha, IL-17 and IL-6) will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

  4. Occurrence of infections [ Time Frame: Baseline up to 48 weeks ]
    Number of participants with infectious adverse events

  5. Pharmacokinetics (Systemic Clearance and central volume of distribution) [ Time Frame: Baseline up to 48 weeks ]
    Rituximab concentrations will be measured at baseline, will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48). Pharmacokinetics will be described using a two-compartment model.

  6. FCGR3A 156 F/V gene polymorphism [ Time Frame: Baseline ]
    FCGR3A 156 F/V gene genotyping. Measurements will be carried out at baseline.

  7. RNA [ Time Frame: Baseline ]
    Gene expression will be analysed at baseline.

  8. Metabolomic profil [ Time Frame: Baseline up to 16 weeks ]
    Urines will be analysed at baseline, week 4 and week 16



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • RA according to the American College of Rheumatology (ACR) criteria
  • Treatment with adalimumab in accordance to the SPC
  • Disease modifying anti rheumatic drugs (DMARDs) stable 4 weeks before enrollment and during 16 weeks.
  • Signed consent

Exclusion Criteria:

  • No anti TNF-alpha failure or contraindication
  • Previous adalimumab treatment
  • Contraindication to adalimumab, methylprednisolone or methotrexate (when used in combination with adalimumab)
  • methotrexate-naive patient
  • Any hematologic disease affecting the lymphocytes (in particular lymphomas)
  • Any osteo-articular disease which could interfere with the interpretation of the influence of the rituximab on RA

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02304354


Contacts
Contact: Denis MULLEMAN, MD-PhD 02.47.47.59.17 ext +33 mulleman@med.univ-tours.fr
Contact: Yoann DESVIGNES 02.47.47.46.32 ext +33 yoann.desvignes@med.univ-tours.fr

Locations
France
Rhumatologie, CHRU de BREST Recruiting
Brest, France, 29609
Contact: Valérie DEVAUCHELLE, MD-PhD         
Principal Investigator: Valérie DEVAUCHELLE, MD-PhD         
Rhumatologie, CHD LA ROCHE SUR YON Recruiting
La Roche Sur Yon, France, 85925
Contact: Grégoire CORMIER, MD         
Principal Investigator: Grégoire CORMIER, MD         
Rhumatologie, CHR du MANS Recruiting
Le Mans, France, 72037
Contact: Emmanuelle DERNIS, MD         
Principal Investigator: Emmanuelle DERNIS, MD         
Rhumatologie, CHRU de NANTES Recruiting
Nantes, France, 44093
Contact: Benoit LE GOFF, MD         
Principal Investigator: Benoit LE GOFF, MD         
Rhumatologie / IPROS, CHR d'ORLEANS Recruiting
Orleans, France, 45000
Contact: Carine SALLIOT, MD         
Principal Investigator: Carine SALLIOT, MD         
Rhumatologie, CHRU de POITIERS Recruiting
Poitiers, France, 86021
Contact: Elisabeth SOLAU-GERVAIS, MD-PhD         
Principal Investigator: Elisabeth SOLAU-GERVAIS, MD-PhD         
Rhumatologie, CHRU de RENNES Not yet recruiting
Rennes, France, 35203
Contact: Aleth PERDRIGER, MD-PhD         
Principal Investigator: Aleth PERDRIGER, MD-PhD         
Rhumatologie, CHRU de TOURS Recruiting
Tours, France, 37044
Contact: Denis MULLEMAN, MD-PhD         
Principal Investigator: Denis MULLEMAN, MD-PhD         
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: Denis MULLEMAN, MD-PhD CHRU de TOURS

Publications:
Responsible Party: University Hospital, Tours
ClinicalTrials.gov Identifier: NCT02304354     History of Changes
Other Study ID Numbers: PHRI13-JM/LYRITUX
2014-000859-91 ( EudraCT Number )
2014-R24 ( Other Identifier: CPP )
140896A-32 ( Other Identifier: ANSM )
First Posted: December 1, 2014    Key Record Dates
Last Update Posted: October 26, 2017
Last Verified: October 2017

Keywords provided by University Hospital, Tours:
rheumatoid arthritis
T lymphocytes
rituximab

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents