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IL-2 for Multi Drug Resistant Nephrotic Syndrome

Information source: Istituto Giannina Gaslini
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Nephrotic Syndrome

Intervention: Proleukin® (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Istituto Giannina Gaslini

Official(s) and/or principal investigator(s):
Gian Marco Ghiggeri, MD, Principal Investigator, Affiliation: Istituto Giannina Gaslini

Summary

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).

Clinical Details

Official title: Use of IL-2 for Pediatric, Multi Drug Resistant, Idiopathic Nephrotic Syndrome

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Proteinuria

Secondary outcome:

Tregs Levels

Serum Creatinine

Adverse events

Eligibility

Minimum age: 2 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

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

Locations and Contacts

Istituto Giannina Gaslini, Genova 16147, Italy
Additional Information

Related publications:

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Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143. Erratum in: N Engl J Med. 2014 Feb 20;370(8):786.

Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP 3rd, Armand P, Cutler C, Ho VT, Treister NS, Bienfang DC, Prasad S, Tzachanis D, Joyce RM, Avigan DE, Antin JH, Ritz J, Soiffer RJ. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. 2011 Dec 1;365(22):2055-66. doi: 10.1056/NEJMoa1108188.

Bertelli R, Trivelli A, Magnasco A, Cioni M, Bodria M, Carrea A, Montobbio G, Barbano G, Ghiggeri GM. Failure of regulation results in an amplified oxidation burst by neutrophils in children with primary nephrotic syndrome. Clin Exp Immunol. 2010 Jul 1;161(1):151-8. doi: 10.1111/j.1365-2249.2010.04160.x. Epub 2010 May 19.

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Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L, Benetti E, Scozzola F, Pasini A, Dallera N, Sica F, Belingheri M, Scolari F, Ghiggeri GM. Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. 2011 Jun;6(6):1308-15. doi: 10.2215/CJN.09421010. Epub 2011 May 12.

Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F, Bodria M, Caridi G, Wei C, Belingheri M, Ghio L, Merscher-Gomez S, Edefonti A, Pasini A, Montini G, Murtas C, Wang X, Muruve D, Vaglio A, Martorana D, Pani A, Scolari F, Reiser J, Ghiggeri GM. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. 2013 Nov;84(5):1025-33. doi: 10.1038/ki.2013.211. Epub 2013 Jun 5.

Caridi G, Bertelli R, Di Duca M, Dagnino M, Emma F, Onetti Muda A, Scolari F, Miglietti N, Mazzucco G, Murer L, Carrea A, Massella L, Rizzoni G, Perfumo F, Ghiggeri GM. Broadening the spectrum of diseases related to podocin mutations. J Am Soc Nephrol. 2003 May;14(5):1278-86.

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Starting date: February 2012
Last updated: May 27, 2015

Page last updated: August 23, 2015

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