Value of Rituximab in Humoral Chronic Rejection After Renal Transplantation (Rituximab 2006)

This study has been terminated.
(lacking recruitment)
Sponsor:
Collaborators:
Humboldt-Universität zu Berlin
University of Erlangen-Nürnberg
University Hospital, Essen
University Hospital Freiburg
Heidelberg University
University of Jena
Transplantationszentrum Köln-Merheim
University of Regensburg
Heinrich-Heine University, Duesseldorf
Martin-Luther-Universität Halle-Wittenberg
Information provided by:
Technische Universität München
ClinicalTrials.gov Identifier:
NCT00568477
First received: December 5, 2007
Last updated: September 30, 2009
Last verified: January 2008
  Purpose

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.


Condition Intervention Phase
Grafting
Renal Transplantation
Transplantation, Kidney
Chronic Allograft Nephropathy
Drug: MabThera
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Open, 2-arm National Multi-center Study to Evaluate the Value of Rituximab in Humoral Chronic Rejection After Renal Transplantation.

Resource links provided by NLM:


Further study details as provided by Technische Universität München:

Primary Outcome Measures:
  • Primary objective: To evaluate the benefit of Rituximab in patients with CAN with histologically proven C4d deposits and/or B-Lymphocyte (CD20+ cells) infiltration of their grafts. Secondary objectives: Renal function at 1 year [ Time Frame: Graft survival at 1 and 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Renal function at 1 year [ Time Frame: Graft survival at 1 and 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: December 2007
Estimated Study Completion Date: December 2010
Arms Assigned Interventions
Experimental: Arm 1
Treatment with rituximab
Drug: 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

No Intervention: Arm 2
Treatment without rituximab

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00568477

Locations
Germany
Technical University of Munich
Munich, Bavaria, Germany, 81675
Sponsors and Collaborators
Technische Universität München
Humboldt-Universität zu Berlin
University of Erlangen-Nürnberg
University Hospital, Essen
University Hospital Freiburg
Heidelberg University
University of Jena
Transplantationszentrum Köln-Merheim
University of Regensburg
Heinrich-Heine University, Duesseldorf
Martin-Luther-Universität Halle-Wittenberg
Investigators
Principal Investigator: Uwe Heemann, Prof. MD Technical University of Munich, Klinikum rechts der Isar; Münchner Studienzentrum
  More Information

No publications provided

Responsible Party: Univ.-Prof. Dr. med. Dr. h.c. Uwe Heemann, Technical University of Munich, Klinikum rechts der Isar
ClinicalTrials.gov Identifier: NCT00568477     History of Changes
Other Study ID Numbers: VAL-518-HEE-0200-S, EudraCT-number: 2006-006137-41
Study First Received: December 5, 2007
Last Updated: September 30, 2009
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität München:
Rituximab, Heemannn

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 26, 2014