De Novo Everolimus-based Therapy for Renal Transplantation Using Rituximab Induction

NCT01312064 | Terminated Phase 4

• 1 other identifier: 201011050MB
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesized that everolimus-based immunosuppressive therapy combined with rituximab induction could provide comparable safety profiles for renal transplant patients, as compared to standard immunosuppressive therapy using thymoglobulin induction, tacrolimus, mycophenolate mofetil and steroids, in terms of acute rejection rate and renal function. Rituximab was reported to reverse refractory acute kidney transplant rejection. Combined with immunoadsorption with or without IVIG, rituximab could successfully prevent antibody-mediated rejection in ABO-incompatible renal transplantation. This study is to assess whether a CNI-free regimen including B-cell depleting antibody induction, everolimus and MMF results in comparable long-term function without a negative impact on safety or efficacy of immunosuppression. This study will be open-label and two-arm randomized (2:1).

Conditions

Renal Insufficiency

Keywords

rituximab; everolimus

Outcome Measures

Primary Outcomes (1)

• acute rejection

  The log-rank test will be used to analyse the percentage of rejection-free survival between the two groups. Any patient with a suspicious rejection episode will reveive renal biopsy.

  6 months

Secondary Outcomes (2)

• renal function

  24 months

• adverse event

  24 months

Study Arms (2)

rituximab and everolimus

ACTIVE COMPARATOR

Patients of the study arm will receive rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus will be given with an initial dose of 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation.

Drug: rituximab and everolimus

thymoglobulin and tacrolimus

ACTIVE COMPARATOR

The control arm will receive thymoglobulin induction and tacrolimus-based immunosuppressive therapy. The dose of thymoglobulin would be 1.0mg/kg/d for 3 days25. The first dose of thymoglobulin will be administered before graft kidney reperfusion, and so is rituximab. All patients will receive corticosteroid therapy as usual. The initial daily dose of tacrolimus will be 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation. The doses of tacrolimus will be adjusted to target the whole blood trough levels between 8 to 12 ng/ml during the first 30 days after transplantation, and tapered to 6 to 10 ng/ml at 6 months.

Drug: thymoglobulin and tacrolimus

Interventions

rituximab and everolimus DRUG

rituximab (375mg/m2) induction and subsequently everolimus-based immunosuppressive therapy. Everolimus initial dose: 1 mg bid within 24 hrs after reperfusion, adjusted to a target trough blood level of 6-10 ng/ml for the first 6 months after transplantation.

Also known as: mabthera

rituximab and everolimus

thymoglobulin and tacrolimus DRUG

thymoglobulin induction and tacrolimus-based immunosuppressive therapy. thymoglobulin dose: 1.0mg/kg/d for 3 days daily dose of tacrolimus: 0.15 mg/kg/d given in two doses starting within 24 hours after transplantation

Also known as: ATG

thymoglobulin and tacrolimus

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients at 15-65 years of age undergoing renal transplantation
• Patients who have been informed of the potential risks and side effects of the study
• Patients who have given written informed consent to participate in the study
• Females who are not pregnant or nursing women (pregnancy test required)

You may not qualify if:

• Donor age greater than 65 years
• Patients receiving a perfectly matched kidney (6 matches HLA A, B, DR)
• Patients who are recipients of multiple solid organ transplants
• Patients undergoing second or subsequent transplantation
• Patients with pre-transplant PRA \> 30%
• Patients with ABO incompatibility or positive lymphocytotoxicity
• Patients with severe, active infection
• Patients who have an abnormal liver profile such as ALT, AST, alkaline phosphatase or total bilirubin \>3 times the upper normal limit
• Patient who are HIV-positive or hepatitis C (PCR+ only) B surface antigen positive
• Patients who have been treated with an investigational drug or therapy within one month prior to entry or who will be so treated within 6 months of transplantation
• Patients with a history of malignancy within the last five years except excised squamous or basal cell carcinoma
• Patients with a history of alcohol or drug abuse or signs of alcohol-induced organ damage, mental dysfunction or other factors limiting their ability to comply fully with the study requirements.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Rituximab; Everolimus; thymoglobulin; Tacrolimus

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• MK Tsai, MD, PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2011
• First Posted: March 10, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: December 27, 2012

Record last verified: 2012-11

Locations

TW (1)