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

Children's Hospital Medical Center, Cincinnati23 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Thrombotic Microangiopathies Atypical Hemolytic Uremic Syndrome

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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.

Locations (3)

Children's Hospital Los Angeles (CHLA)

Los Angeles, California, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Survival

Survival at 6 months after the date of TMA diagnosis

Time frame: 6 months

Secondary Outcomes

Number of Participants With Organ Dysfunction

Number of participants with organ dysfunction at 6 months after TMA diagnosis. Organ dysfunction definitions are listed in the protocol Appendix II that is uploaded to ClinicalTrials.gov site.

Time frame: 6 months

Number of Participants With Organ Dysfunction

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.

Time frame: 1 year

Non-relapse Mortality

Non-relapse mortality descriptively compared with historical controls at 1 year