Efficacy of Rituximab in Acute Cellular Rejection in Renal Transplant Patients

NCT ID: NCT01117662

Last Updated: 2018-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2016-08-23

Brief Summary

Acute kidney allograft rejection is the major cause for a loss of graft function and has a negative impact on long-term graft survival. Anti-rejection therapy traditionally focuses on T cell-mediated mechanisms of renal allograft rejection. However, available agents that affect T-cell pathways have only little impact on long-term graft survival. There is increasing evidence that B-cells play an important role in acute transplant rejections. CD20+ B cell infiltrates in acute T-cell mediated rejections are frequent and correlate with a worse response to conventional anti-rejection treatment and an increased risk of graft loss. In one pilot study, supported by several case reports, a beneficial effect of Rituximab for the treatment of acute rejection episodes with intrarenal B-cell infiltrates was shown. However, despite the promise of these observations solid evidence is required before incorporating this treatment option into a general treatment recommendation.

In a multicenter randomized placebo controlled double blind phase III trial the investigators want to demonstrate that Rituximab in addition to standard treatment with steroid-boli is superior to the standard treatment alone regarding long-term kidney function. If the proposed study proves that Rituximab treatment of acute rejections is beneficial for the long-term allograft function, the conventional rejection therapy needs to be revised to this novel concept of B- cell targeting

Conditions

Acute Rejection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Rituximab

Intravenous application of Rituximab 375mg/m² body surface in 250 ml NaCl 0,9 % over 4 hours

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Intravenous application of Rituximab 375mg/m² body surface in 250 ml NaCl 0,9 % over 4 hours

Control

Intravenous application of placebo (NaCl 0,9 %) matching active treatment

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous application of placebo (NaCl 0,9 %) matching active treatment

Interventions

Rituximab

Intravenous application of Rituximab 375mg/m² body surface in 250 ml NaCl 0,9 % over 4 hours

Intervention Type: DRUG

Placebo

Intravenous application of placebo (NaCl 0,9 %) matching active treatment

Intervention Type: DRUG

Other Intervention Names

MabThera

Eligibility Criteria

Inclusion Criteria

1. male or female patients age ≥ 18 at the time of the inclusion in the study

2. male or female patients after kidney transplantation if medically justifiable (cave: previous immunosuppression, particularly prior induction therapies or biologicals).

3. Proof of an acute rejection in kidney transplant according to Banff-criteria: T-cell-mediated rejection as borderline, grade IA/B, IIA/B (no v-only), if one or more results are available as significant B-cell infiltrates CD20≥20 / high power field, glomerulitis, peritubular capillaritis or C4d positivity (with the exception of ABO-incompatible transplantations) as well as patients who have no T-cell-mediated acute rejection, but signs of acute humoral rejection (as listed above according to the criteria glomerulitis, peritubular capillaritis, C4d positivity) who have to be treated according to medical opinion of the physician with steroid therapy. The evidence of rejection can be performed by a protocol or indication biopsy.

4. SV40-negativity in the biopsy

5. GFR calculated using the MDRD-Formula > 25 ml/min/1,73 m² in the time period before the noticed rejection.

6. Presence of a negative pregnancy test and consent to a highly effective contraceptive method (i.e. failure rate less than 1% per year, which are implants, injectable contraceptives, combined oral contraceptives, intrauterine devices (only hormone spirals), sexual abstinence or vasectomy of the partner) in patients of child-bearing age. This is not required when bilateral sterilization or ovariectomy of the patient and in patients that have exclusively female sex partners. Presence of consent to a highly effective contraceptive method for male patient.

7. Informed consent

Exclusion Criteria

1. Known contraindications, resp. incompatibility for Rituximab and/or for the concomitant medication

2. Administration of Rituximab within the last 12 months before inclusion

3. Simultaneous participation in an other clinical study or participation in an other clinical study within the last 30 days

4. Breastfeeding women or pregnant women

5. Persons who fail to assess essence, meaning and significance of the clinical study and act along these lines (according to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG)

6. Existence of an active CMV-infection, existence of a HIV-infection, existence of a replicative hepatitis B or C, existence of other grave infections

7. Cardiac insufficiency in phase NYHA III-IV

8. High grade cardiac arrhythmias

9. Unstable coronary heart disease

10. Poorly adjusted diabetes mellitus (HbA1c > 10 %) at the time of the inclusion in the study.

11. State after splenectomy

12. Contra-indication referring to a renewed transplant biopsy (e.g. coagulopathy, anticoagulation)

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

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Hannover Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hannover Medical School

Hanover, Lower Saxony, Germany

Universitätsklinikum der RWTH Aachen Medizinische Klinik II

Aachen, , Germany

Charité Campus Mitte Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Köln Medizinische Klinik IV Nephrologie

Cologne, , Germany

Kliniken der Stadt Köln gGmbH Medizinische Klinik I

Cologne, , Germany

Universitätsklinikum Düsseldorf Klinik für Nephrologie

Düsseldorf, , Germany

Universitätsklinikum Erlangen Nephrologie und Hypertensiologie

Erlangen, , Germany

Universitätsklinikum Essen Klinik für Nephrologie

Essen, , Germany

Universitätsklinikum Freiburg Medzinische Klinik IV Nephrologie Freiburg

Freiburg im Breisgau, , Germany

Nephrologisches Zentrum Niedersachsen 34346 Hannoversch Münden

Hannoversch Münden, , Germany

Universitätsklinikum Jena Klinik für Innere Medizin III

Jena, , Germany

Universitätsklinikum Schleswig-Holstein Campus Kiel Klinik für Nieren- und Hochdruckkrankheiten Kiel

Kiel, , Germany

Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Uniklinik München Klinikum Großhadern

München, , Germany

Universitätsklinikum Münster Innere Medizin / Nephrologie

Münster, , Germany

Countries

Germany

References

Schiffer L, Schiffer M, Merkel S, Schwarz A, Mengel M, Jurgens C, Schroeder C, Zoerner AA, Pullmann K, Brocker V, Becker JU, Dammrich ME, Trader J, Grosshennig A, Biertz F, Haller H, Koch A, Gwinner W. Rationale and design of the RIACT-study: a multi-center placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients: study protocol for a randomized controlled trial. Trials. 2012 Oct 26;13:199. doi: 10.1186/1745-6215-13-199.

Reference Type: DERIVED

PMID: 23101480 (View on PubMed)

Other Identifiers

200710602

Identifier Type: -

Identifier Source: org_study_id