Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients

Sponsor
Children's Hospital Medical Center, Cincinnati (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03518203
Collaborator
(none)
23
3
1
63.9
7.7
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Study Details

Study Description

Brief Summary

Hematopoietic stem cell transplantation (HCT)-associated thrombotic microangiopathy (TMA) is an understudied complication of HCT that significantly affects transplant related morbidity and mortality. The investigators hypothesize that early intervention with complement blocker eculizumab will double survival in HCT recipients with high risk TMA, as compared to historical untreated controls. An optimal eculizumab dosing schedule can be determined for this population through eculizumab pharmacokinetic/pharmacodynamic (PK/PD) testing.

Detailed Description

This clinical trial is a prospective single arm multi-institution study in children and young adults undergoing allogeneic or autologous hematopoietic stem cell transplantation who will receive early therapy with eculizumab to prevent TMA-associated MODS after transplantation. The purpose of this research study is to examine efficacy of complement blocker eculizumab in HCT recipients with high risk TMA and to determine optimal eculizumab dosing regimen for HCT recipients with TMA using PK/PD studies. All patients will receive therapy based on their weight for 24 weeks. Survival will be assessed at 6 months from TMA diagnosis.

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Early Intervention With Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome (TMA/aHUS)-Associated Multiple Organ Dysfunction Syndrome (MODS) in Hematopoietic Stem Cell Transplant (HCT) Recipients
Actual Study Start Date :
Aug 3, 2018
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Eculizumab

All patients will receive eculizumab based on their weight for 24 weeks.

Drug: Eculizumab
Eculizumab will be administered as intravenous infusion (IV) over 60 minutes. The dosage form will be 300 mg single-use vials each containing 30 mL of 10 mg/mL sterile, preservative-free solution.
Other Names:
  • Soliris
  • Outcome Measures

    Primary Outcome Measures

    1. Survival [6 months]

      Survival at 6 months after the date of TMA diagnosis

    Secondary Outcome Measures

    1. Incidence of organ dysfunction [6 months]

      Incidence of organ dysfunction at 6 months after TMA diagnosis

    2. Incidence of organ dysfunction [1 year]

      Incidence of organ dysfunction at 1 year after TMA diagnosis

    3. Time to resolution of organ dysfunction [1 year]

      Timing of resolution of organ dysfunction in the first year after therapy. Resolution of organ dysfunction is assessed based on protocol-defined multiple organ dysfunction syndrome criteria.

    4. Non-relapse mortality [1 year]

      Non-relapse mortality compared with historical controls at 1 year

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients of any age undergoing allogeneic or autologous HCT

    • Histologic TMA diagnosis OR clinical TMA diagnosis and presenting with high risk disease features including elevated plasma sC5b-9 above laboratory normal value (≥244ng/ml) and proteinuria measured as ≥30mg/dL of protein on random urinalysis x2 or protein/creatinine ratio ≥1mg/mg or patient receiving renal replacement therapy.

    • Minimum weight of ≥ 5kg.

    Exclusion Criteria:
    • Known hypersensitivity to any constituent of the study medication.

    • Subjects with unresolved serious Neisseria meningitides infection or progressive severe infection.

    • Patients with diagnosis of TTP as defined by ADAMST13 activity test <10%.

    • Patients previously treated with eculizumab or other complement blocker for TMA within the 60 days prior to first dose of study treatment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Children's Hospital Los Angeles (CHLA) Los Angeles California United States 90027
    2 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    3 Children's Hospital of Philadelphia (CHOP) Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Children's Hospital Medical Center, Cincinnati

    Investigators

    • Principal Investigator: Sonata Jodele, MD, Children's Hospital Medical Center, Cincinnati

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Children's Hospital Medical Center, Cincinnati
    ClinicalTrials.gov Identifier:
    NCT03518203
    Other Study ID Numbers:
    • 2018-7119C
    First Posted:
    May 8, 2018
    Last Update Posted:
    Dec 14, 2021
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Children's Hospital Medical Center, Cincinnati
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 14, 2021