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Reduce Immunosuppression With Atmp in NS ChildrEn (RACE)

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ClinicalTrials.gov Identifier: NCT04034316
Recruitment Status : Enrolling by invitation
First Posted : July 26, 2019
Last Update Posted : February 5, 2020
Sponsor:
Collaborators:
Cell Factory Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Laboratorio Sperimentale di Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione IRCCS Policlinico S. Matteo, Pavia
Information provided by (Responsible Party):
Giovanni Montini, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary:

A phase II open-label, single arm study aimed to ascertain whether infusions of cord-blood mesenchymal stromal cells (CB-MSCs) allow to reduce or suspend the chronic immunosuppressive therapy (IS) in steroid-dependent nephrotic syndrome (SDNS).

We plan to enroll 11 patients aged 3 to 18 with SDNS in remission for at least one month, maintained by either ≥2 immunosuppressive drugs or a calcineurin inhibitor.

Patients are infused with cord-blood allogenic MSC, selected by in-vitro alloreactivity, at a dose of 1.5x10^6/kg on days 0, 14, 21. The immunosuppressive treatment is gradually tapered starting at the first CB-MSC administration, according to the following scheme: 25% following the first administration, 50% following the second administration, and 100% reduction following the third administration.

All patients will be followed-up for 6 months from the last CB-MSC. Study visits are planned at baseline during CB-MSC administrations, 2 weeks (follow-up [FU]1) and 6 weeks (FU2) after the last infusion, and then every 6 weeks. During follow-up, the patients undergo a physical examination (including measurement of height, weight and blood pressure) and laboratory evaluations (urinary protein:urinary creatinine ratio, complete blood count, kidney function, plasma proteins, liver function, triglycerides and cholesterol). In addition, a blood sample is taken for regulatory T lymphocyte quantification, a marker of clinical response to the infusions.


Condition or disease Intervention/treatment Phase
Nephrotic Syndrome in Children Steroid-Dependent Nephrotic Syndrome Idiopathic Nephrotic Syndrome Other: Cord-blood mesenchymal stromal cells Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-label Study to Evaluate the Efficacy of Allogeneic Human Cord Blood-derived Mesenchymal Stromal Cells in Maintaining Remission After Immunosuppressive Therapy Withdrawal in Pediatric Patients With Steroid-dependent Nephrotic Syndrome
Actual Study Start Date : November 2, 2018
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MSC

During the first part of the study, 11 SDNS pediatric patients will receive 3 intravenous infusions of CB-MSCs at the dosage of 1.5 x 10^6/kg at a time interval of 1 to 2 weeks. The ongoing immunosuppressive treatment will be gradually tapered off after the first CB-MSC administration, as follows:

  • 25% reduction of the ongoing immunosuppressive treatment following the first administration;
  • 50% reduction of the ongoing immunosuppressive treatment following the second administration;
  • interruption of the ongoing immunosuppressive treatment following the third administration.

In the case that the hypothesis that P ≥ 0.600 is rejected and therefore the second part of the study will be required, 11 additional pediatric patients with SDNS will be treated with 3 intravenous infusions of CB-MSCs at the dosage of 2x10^6/kg at a time interval of 1 to 2 weeks.

Other: Cord-blood mesenchymal stromal cells
The product is packaged in bags suitable for the cryopreservation of cell products. Before administration the cells must be thawed and diluted in an appropriate vol:vol solution: made by saline 78%, human albumin 10%, Acyl-CoA dehydrogenase-A (ACD-A) 12%.




Primary Outcome Measures :
  1. The percentage of patients without nephrotic syndrome recurrence after complete withdrawal of immunosuppressive treatment for at least 6 months [ Time Frame: 6 months following completion of the intervention ]
    The percentage of patients without nephrotic-range proteinuria as measured by the urinary protein to urinary creatinine ratio (uPr/uCr<2) 6 months after completing the intervention


Secondary Outcome Measures :
  1. The percentage of adverse events [ Time Frame: 6 months following completion of the intervention ]
    As described by the Common Terminology Criteria for Adverse Events

  2. The time to recurrence of nephrotic syndrome [ Time Frame: Within 6 months from the completion of the intervention ]
    As measured by the ratio of urinary protein to urinary creatinine

  3. The percentage of participants achieving a reduction in the immunosuppressive therapy [ Time Frame: 6 months following completion of the intervention ]
    Reduction of the ongoing immunosuppressive treatment

  4. The dose of immunosuppressive therapy to prevent further NS relapses [ Time Frame: 6 months following completion of the intervention ]
    The minimal dose of immunosuppressive therapy necessary to maintain the patient in remission following the therapy

  5. Reported Quality of Life [ Time Frame: 6 months following completion of the intervention ]
    Changes in quality of life as reported by the patients and/or parents



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 3 and 18 years;
  2. Clinical diagnosis of SDNS;
  3. Disease remission maintained by chronic therapy (at least 6 months) with either:

    • Use of a combination of 2 or more immunosuppressive drugs
    • use of 1 of the calcineurin inhibitors (Cyclosporin or Tacrolimus);
  4. Absence of proteinuria (PrU/CrU < 0.2 mg/mg) for at least 1 month;
  5. eGFR greater than or equal to 70 ml/min/1.73 m^2;
  6. Written informed consent from parents or guardians and the child when possible

Exclusion Criteria:

  1. Age < 3 years or > 19 years;
  2. Resistant/refractory NS;
  3. Presence of genetic mutations associated with NS;
  4. eGFR less than 70 ml/min/1.73m2;
  5. Thrombophilic condition;
  6. Pregnancy or lactating;
  7. Evidence of an uncooperative attitude;
  8. Any evidence that the patient will be unable to complete the trial follow-up.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04034316


Locations
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Italy
Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan
Milan, MI, Italy
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Cell Factory Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Laboratorio Sperimentale di Immunologia e Trapianti, Oncoematologia Pediatrica, Fondazione IRCCS Policlinico S. Matteo, Pavia

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Responsible Party: Giovanni Montini, Professor, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT04034316    
Other Study ID Numbers: AIFA-2016-02364896
2018-001162-42 ( EudraCT Number )
First Posted: July 26, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Giovanni Montini, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico:
Mesenchymal Stromal Cells
Steroid Dependent Nephrotic Syndrome in Children
Proteinuria
Immunosuppressive treatment
Additional relevant MeSH terms:
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Nephrotic Syndrome
Nephrosis
Syndrome
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs