Value of Rituximab in Humoral Chronic Rejection After Renal Transplantation

NCT ID: NCT00568477

Last Updated: 2009-10-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2010-12-31

Brief Summary

To evaluate the benefit of rituximab in patients with CAN with histologically proven C4d deposits and/or plasma cell and/or B-Lymphocyte (CD20+ cells) infiltration of their grafts.

Detailed Description

This study is a prospective, randomized, open, 2-arm, national multi-center study to evaluate the value of rituximab in humoral chronic rejection after renal transplantation in approximately 150-200 patients (75-100 patients each group).

All biopsies will be analysed by Prof. Groene (Heidelberg) and the results immediately communicated to the central managing unit (Munich). Upon receipt, patients with biopsy proven CAN with C4d+ and/or plasma-cells and/or B-lymphocytes within the last 4 weeks before inclusion (centrally confirmed), fulfilling the inclusion/exclusion criteria, will be randomized 1:1 into one of the 2 groups:

Arm 1: Treatment with rituximab Arm 2: Treatment without rituximab Recruitment will last for approximately one year. All patients will be treated with baseline medication of Tacrolimus, MMF, steroids (optional, with same dose as given before study entry) and ACE-inhibitor or AT1-receptor-antagonist. A single dose of 100 mg Methylprednisolone i.v. will be given at baseline (day 0) in both groups (in the rituximab group 30 min before start of the rituximab infusion).

Each patient will be followed for 1 year within protocol, with study visits at 1,3,7 and 14 days (rituximab group), 3, 6 and 12 months followed by a follow-up period of 1 year with a study visit at 24 months.

Conditions

Grafting; Renal Transplantation; Transplantation, Kidney; Chronic Allograft Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Treatment with rituximab

Group Type: EXPERIMENTAL

MabThera

Intervention Type: DRUG

Rituximab (MabThera):

375 mg/m² as IV infusions over >=6h each at time point 0 and 2 weeks. Initial infusion rate of 50 mg/h, stepwise rise is possible after 30 minutes

Arm 2

Treatment without rituximab

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

MabThera

Rituximab (MabThera):

375 mg/m² as IV infusions over >=6h each at time point 0 and 2 weeks. Initial infusion rate of 50 mg/h, stepwise rise is possible after 30 minutes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Renal allograft recipients at least 1 year after transplantation with GFR > 25 ml/min x 1,73m2 (MDRD)
• Single organ recipients of renal allograft
• Patients who have provided informed consent
• Patients who are >= 18 years of age
• Patients who have biopsy proven CAN with C4d+ deposits and/or plasma-cells and/or B-lymphocytes within the last 4 weeks before inclusion
• Patients who are treated with ACE/AT1 Blocker more than 1 week before inclusion

Exclusion Criteria

• Patients who suffer from HIV infection
• Patients with a history of Hepatitis B
• Patients with Hepatitis C (active/chronic)
• Patients who have a contraindication for the use of rituximab, such as leukopenia or experienced infusion-related adverse events to former antibody treatment
• Patients who showed signs of acute cellular rejection in the biopsy
• Patient has a malignancy or history of malignancy within the last 5 years, except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
• Patient has a systemic infection requiring treatment.
• Female patients who are pregnant or lactating
• Patients who have any form of substance abuse, psychological illness or any other condition, which, in the opinion of the investigator, may interfere with the patient's ability to understand the requirements of the study.
• Patients who have a proteinuria >4g/24h
• Patient is unlikely to comply with the visits scheduled in the protocol.
• Patient is simultaneously participating in another investigational drug study or has participated in such study within 28 days before entry in this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Humboldt-Universität zu Berlin

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg

OTHER

Sponsor Role: collaborator

University Hospital, Essen

OTHER

Sponsor Role: collaborator

University Hospital Freiburg

OTHER

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: collaborator

University of Jena

OTHER

Sponsor Role: collaborator

Transplantationszentrum Köln-Merheim

OTHER

Sponsor Role: collaborator

University of Regensburg

OTHER

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: collaborator

Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Technical University of Munich, Klinikum rechts der Isar

Principal Investigators

Uwe Heemann, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Technical University of Munich, Klinikum rechts der Isar; Münchner Studienzentrum

Locations

Technical University of Munich

Munich, Bavaria, Germany

Countries

Germany

Other Identifiers

EudraCT-number: 2006-006137-41

Identifier Type: -

Identifier Source: secondary_id

VAL-518-HEE-0200-S

Identifier Type: -

Identifier Source: org_study_id