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

Phase 2

Completed

• Conditions: Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome; Multiple Organ Dysfunction Syndrome
• Interventions: Drug: Eculizumab

• Registration Number: NCT03518203
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

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 Timeline

• Study First Submitted: 2018-03-05
• Study First Submitted QC: 2018-05-04
• Study First Posted: 2018-05-08
• Study Start: 2018-08-03
• Primary Completion: 2022-04-04
• Study Completion: 2022-06-01
• Results First Submitted: 2023-05-30
• Status Verified: 2023-08
• Results First Submitted QC: 2023-09-20
• Last Update Submitted: 2023-09-20
• Results First Posted: 2023-09-21
• Last Update Posted: 2023-09-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eculizumab	Eculizumab	All patients will receive eculizumab based on their weight for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Survival	6 months	Survival at 6 months after the date of TMA diagnosis

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Organ Dysfunction	1 year	Number of participants with organ dysfunction at 1 year after TMA diagnosis. Organ dysfunction definitions are listed in the protocol Appendix II that is uploaded to ClinicalTrials.gov site.
Non-relapse Mortality	1 year	Non-relapse mortality descriptively compared with historical controls at 1 year

Trial Locations

Locations (3)

Children's Hospital Los Angeles (CHLA); 🇺🇸 Los Angeles, California, United States

Children's Hospital of Philadelphia (CHOP); 🇺🇸 Philadelphia, Pennsylvania, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States