Clinical trial NCT03518203: Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thrombotic Microangiopathies
Atypical Hemolytic Uremic Syndrome
Multiple Organ Dysfunction Syndrome
Keywords: Hematopoietic Stem Cell Transplant
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2018-05-08
Enrollment: 23
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Survival
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants With Organ Dysfunction
timeFrame: 6 months
measure: Number of Participants With Organ Dysfunction
timeFrame: 1 year
measure: Non-relapse Mortality
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles (CHLA)
state: California
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Sonata Jodele, MD
role: PRINCIPAL_INVESTIGATOR
References: