Study of First Line Treatment of Chronic Graft Versus Host Disease With the Association of Ciclosporine, Corticosteroids and Rituximab (Protocol R-GVHD)

NCT01135641 | Completed Phase 2 DMC

• 2 other identifiers: 09/6-B2009-016898-14
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of the study is to improve the response rate (complete and partial remission) at 12 months after diagnosis of chronic Chronic Graft Versus Host Disease (GVHD) and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

Conditions

Graft Versus Host Disease

Keywords

Adult patients (≥18 years); first allogeneic stem cell transplantation; first episode of chronic GVHD requiring systemic immunosuppressive therapy

Outcome Measures

Primary Outcomes (1)

• Response rate at 12 months

  Response rate (complete and partial remission) at 12 months after diagnosis of chronic GVHD and treatment with the combination of ciclosporine, prednisone and Rituximab as first line treatment.

Secondary Outcomes (4)

• Number of participants with adverse events as a measure of safety and tolerability

• Treatment failure

• Transplant-related mortality

• Quality of life

Study Arms (1)

Rituximab, ciclosporine and corticosteroids

EXPERIMENTAL

As soon as the diagnosis of chronic GVHD requiring systemic immunosuppressive therapy is confirmed, patients will receive in addition to ciclosporine A and corticosteroids (prednisone) 1 mg/kg/day, Rituximab at 375 mg/m²/infusion once a week for 4 consecutive weeks.Rituximab should be administered within 14 days of starting prednisone. Follow-up dates for response assessment and laboratory tests relate to the date of Rituximab infusion.Patients having a partial response after the 1st cycle of Rituximab will be eligible to receive a second cycle of 4 infusions during 4 weeks. A delay of 8 weeks (from the first infusion of Rituximab) will be observed between the two cycles of Rituximab therapy.Patients who relapse after an initial treatment with one cycle of 4 infusions of Rituximab will be eligible to receive a second cycle of Rituximab therapy.

Drug: Rituximab; Drug: Ciclosporine; Drug: Corticosteroids

Interventions

Rituximab DRUG

Patients will receive in addition to ciclosporine A and corticosteroids (prednisone) 1 mg/kg/day, Rituximab at 375 mg/m²/infusion once a week for 4 consecutive weeks.

Rituximab, ciclosporine and corticosteroids

Ciclosporine DRUG

Rituximab, ciclosporine and corticosteroids

Corticosteroids DRUG

Rituximab, ciclosporine and corticosteroids

Eligibility Criteria

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

You may qualify if:

• Adult patients (≥18 years) who have received a first allogeneic stem cell transplantation for a hematological disease
• Confirmed diagnosis of first episode of chronic GVHD requiring systemic immunosuppressive therapy. Chronic GVHD diagnosis is defined according to the NIH Working Group Consensus. Chronic GVHD diagnosis will be based on the evaluation of the severity of the different clinical manifestations including :
• Ocular, oral and mucosal symptoms,
• Performance status evaluation,
• Pulmonary function evaluation,
• Cutaneous evaluation measured by the percentage of extension of manifestations of liche-noid or sclerodermatous aspects, eventually confirmed with a biopsy whenever possible,
• Evaluation of the musculoskeletal manifestations, especially the amplitude of the rele-vant articulations,
• Evaluation of liver involvement (Total bilirubin, Transaminases, Phosphatase alcalines and Gamma GT).
• Any source of hematopoietic stem cells is authorized.
• Any category of conditioning regimen prior to allo-SCT is authorized.
• Any type of stem cell donors is authorized.
• Signed informed consent.
• Any prior GVHD prophylaxis previously used is accepted.
• Absence of contra-indications to the use of Rituximab.
• Subjects affiliated with an appropriate social security system.

You may not qualify if:

• Patient developing acute GVHD (whether early or "late onset" form)
• A "limited" form of chronic GVHD not requiring systemic immunosuppressive therapy
• Treatment with prednisone (or equivalent) at doses higher than 1 mg/kg/day at the time of enrollment.
• GVHD occurring following donor lymphocytes infusion (DLI)
• Not the first episode of chronic GVHD needing systemic immunosuppressive therapy
• Neutropenia \<500/µL
• Second allogeneic stem cell transplant
• Uncontrolled systemic infection which in the opinion of the investigator is associated with an increased risk of the patient's death within 1 month after the start of therapy
• Severe neurological or psychiatric disorders
• Denied informed consent
• Pregnancy

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

Nantes University Hospital

Nantes, 44093, France

Location

Related Publications (1)

• Malard F, Labopin M, Yakoub-Agha I, Chantepie S, Guillaume T, Blaise D, Tabrizi R, Magro L, Vanhove B, Blancho G, Moreau P, Gaugler B, Chevallier P, Mohty M. Rituximab-based first-line treatment of cGVHD after allogeneic SCT: results of a phase 2 study. Blood. 2017 Nov 16;130(20):2186-2195. doi: 10.1182/blood-2017-05-786137. Epub 2017 Sep 1.

  PMID: 28864814 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Rituximab; Cyclosporins; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Mohamad MOHTY, Profesor

  Hôpital Saint-Antoine (Paris)

  PRINCIPAL INVESTIGATOR

• Noël MILPIED, Profesor

  University Hospital, Bordeaux

  STUDY CHAIR

• Mauricette MICHALLET, Profesor

  Hospices Civils de Lyon

  STUDY CHAIR

• Karin BILGER, Doctor

  CHRU de Strasbourg

  STUDY CHAIR

• Oumédaly REMAN, Doctor

  CHRU de Caen

  STUDY CHAIR

• Ibrahim YAKOUB-AGHA, Profesor

  CHRU de Lille

  STUDY CHAIR

• Didier BLAISE, Profesor

  Institut Paoli-Calmettes

  STUDY CHAIR

• Patrice CEBALLOS, Doctor

  CHU de Montpellier

  STUDY CHAIR

• Patrice CHEVALLIER, Doctor

  Nantes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2010
• First Posted: June 3, 2010
• Study Start: June 1, 2010
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 3, 2014

Record last verified: 2014-04

Locations

FR (1)