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

Cincinnati Children's Hospital Medical Center

Status and phase

Completed

Phase 2

Conditions

Multiple Organ Dysfunction Syndrome

Thrombotic Microangiopathies

Atypical Hemolytic Uremic Syndrome

Treatments

Drug: Eculizumab

Study type

Interventional

Funder types

Other

Identifiers

NCT03518203

2018-7119C

Details and patient eligibility

About

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.

Full 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.

Enrollment

23 patients

Sex

All

Volunteers

No Healthy Volunteers

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.