Clinical Trial: Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Prospective, Sequential Study to Assess the Efficacy of Rituximab Therapy in Maintaining Remission of Nephrotic Syndrome After Steroid and Immunosuppressive Therapy Withdrawal in Patients With Stero

Brief Summary:

Background. Patients, especially children, with steroid-dependent or multirelapsing nephrotic syndrome (NS) secondary to minimal change disease (MCD) or idiopathic focal and segmental glomerulosclerosis (FSGS) on continuous treatment with steroids and/or other immunosuppressive agents to limit or prevent recurrences are at increased risk of severe drug-related adverse events. Case reports suggest that Rituximab, a B cell depleting monoclonal antibody, could be a safe and effective alternative to steroid or immunosuppressants to achieve and maintain remission in this population.

Objectives. The study is primarily aimed at evaluating whether Rituximab may maintain stable NS remission after tapering and withdrawal of steroid and immunosuppressive therapy in patients with MCD or FSGS and steroid-dependent or multirelapsing NS. Secondarily, the study will assess whether Rituximab allows reducing maintenance doses of steroids and other immunosuppressants (in those who relapse), thus limiting treatment related side effects and costs.

Methods. This prospective, sequential, open, study will include 20 patients with histology evidence of MCD or FSGS and steroid-dependant or multirelapsing NS, who are on stable complete or partial remission since at least 1 month and, based on their previous history, are expected to invariably relapse after steroid/immunosuppression withdrawal. After baseline evaluation of clinical, laboratory and kidney function parameters [including glomerular filtration rate (GFR), renal plasma flow (RPF), albumin and sodium fractional clearance and the glomerular albumin permeability assay (Palb)], patients will receive one Rituximab infusion that will be repeated 1 week later if CD20 cells are not fully depleted from the circulation. Then ongoing immunosuppression will be progressively tapered up to complete wit

Detailed Summary:

BACKGROUND Nephrotic syndrome (NS)affects 2 every 100,000 children younger than 16 years. Minimal change disease (MCD) accounts for around 90 percent of cases and most of the remaining ones are associated with focal segmental glomerulosclerosis (FSGS). Patients with NS are at increased risk for life-threatening infections and thromboembolic episodes, and are often affected by dyslipidemia and osteoporosis. Glucocorticoids are first-line treatment and may achieve remission in about 90% of patients with MCD and in 20 to 60% of those with FSGS. In about 20% to 60% of those achieving remission, however, steroid withdrawal is followed by a recurrence of the disease. These patients require chronic steroid therapy (steroid-dependent cases): this prevents relapses in most cases but is invariably associated with severe adverse effects including growth retardation, infections, malignancies, hypertension, impaired glucose tolerance, weight gain and somatic changes. In a small proportion of patients, recurrences occur even under chronic steroid therapy (multirelapsing cases). In these cases, several approaches have been used to control disease activity including plasmapheresis and add-on therapy with cyclophosphamide, cyclosporine, mycophenolate mofetil and other immunosuppressants. Chronic immunosuppression, however, seldom achieves persistent remission and is invariably burdened by serious adverse effects including gonadotoxicity and sterility, opportunistic infections, malignancies, bone marrow depression and renal toxicity. Thus, safer and more effective treatments are urgently needed for these patients.

Rituximab, a chimeric monoclonal antibody targeted to the CD20 antigen of B cells able to induce antibody-dependent and complement-mediated lysis of these cells, has been reported to be effective in children with NS secondary to MCD or FSGS unresponsive to other immunosuppressive
Sponsor: Mario Negri Institute for Pharmacological Research

Current Primary Outcome: Recurrence of NS. [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 month. ]

Original Primary Outcome: Same as current

Current Secondary Outcome: The dose of immunosuppressive therapy to prevent further NS relapses. Adverse effects of immunosuppressive therapy, such as arterial hypertension and need for antihypertensive therapy, impaired glucose tolerance, dyslipidemia, renal dysfunction. Kidney [ Time Frame: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 month. ]

Original Secondary Outcome: Same as current

Information By: Mario Negri Institute for Pharmacological Research

Dates:
Date Received: September 21, 2009
Date Started: April 2009
Date Completion:
Last Updated: February 22, 2013
Last Verified: February 2013