IL-2 for Multi Drug Resistant Nephrotic Syndrome

Istituto Giannina Gaslini5 enrolled

Overview

The aim of the study is to design an open-label phase 1-2 trial to assess safety and clinical and immunologic effects of repeated administration of recombinant low dose IL2 (Proleukin) in 5 patients with idiopathic nephrotic syndrome unresponsive to drugs (steroids, calcineurin inhibitors, Rituximab), following the therapeutical scheme indicated for crioglobulinemic nephropathy: cycle1: IL2 1x106 /m2 s.c for 5 consecutive days cycle2: IL2 1.5 x106 / m2 s.c for 5 consecutive days, starting from 3 weeks after the first cycle. cycle3: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 6 weeks after the first cycle. Cycle 4: IL2 1.5 x106 /m2 s.c for 5 consecutive days, starting from 9 weeks after the first cycle. Current therapy with steroids and calcineurin inhibitors (Prograf) will be maintained during the first cycle and progressively reduced during the subsequent cycles. The first cycle will be performed during hospitalization in the investigators Unit; subsequent cycles will be performed at nephrology outpatients. All laboratory values normally utilized in the follow up of patients affected by idiopathic nephrotic syndrome will be evaluated during the first week of treatment and at the end of the protocol, together with specific cellular values (Tregs, B cells, NK).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Nephrotic Syndrome

Eligibility

Sex: ALLMin age: 2 YearsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Drug resistance: persistence of proteinuria in nephrotic range after a cycle of steroids of at least 3 months and an association with cyclosporine/tacrolimus for at least other 6 months * Parents'/guardian's written informed consent, and child's assent given before any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care. * Age between 2 and 18 years * Histological pattern of minimal change disease, mesangial proliferation with IgM deposits or focal segmental glomerulosclerosis Exclusion Criteria: * Positivity to autoimmunity tests (ANA, dsDNA, ANCA). * Reduction of C3 levels. * Hystological pattern characterized by elements suggestive for congenital disease: diffuse mesangial sclerosis without IgM deposits, cystic-like tubular dilatation, mitochondrial abnormalities evident on electron microscopy, IF suggestive for congenital collagen 4 disease. * Histological pattern not suitable with INS in the pediatric age (membranous glomerulonephritis, lupus nephritis, diffuse and/or localized vasculitis, amyloidosis) * Homozygous or heterozygous mutations of to the 3 genes (NPHS1, NPHS2, WT1) whose mutations are known to be responsible of almost 80% of familiar cases

Outcomes

Primary Outcomes

Proteinuria

Complete remission is defined by urinary protein/creatinine ratio (uPCR) \<200 mg/g (\<20mg/mmol) for 3 consecutive days. Partial remission is defined as proteinuria reduction of 50% or greater from the presenting value and absolute uPCR between 200 and 2000 mg/g. for 3 consecutive days.

Time frame: Change from baseline at 30, 60 and 180 days after first cycle (5 days)

Secondary Outcomes

Tregs Levels

Time frame: Immediately before first cycle and 30, 60 and 180 days after first cycle (5 days)

Serum Creatinine

Time frame: Change from baseline at 30, 60 and 180 days after first cycle (5 days)

Adverse events

Time frame: From day 1 to day 5 of each cycle. The study includes 5 cycles, each one lasting 5 days.