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

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

Sponsors

Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Source 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.

Overall Status Recruiting
Start Date August 3, 2018
Completion Date December 2023
Primary Completion Date December 2022
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Survival 6 months
Secondary Outcome
Measure Time Frame
Incidence of organ dysfunction 6 months
Incidence of organ dysfunction 1 year
Time to resolution of organ dysfunction 1 year
Non-relapse mortality 1 year
Enrollment 21
Condition
Intervention

Intervention Type: Drug

Intervention Name: Eculizumab

Description: 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.

Arm Group Label: Eculizumab

Other Name: Soliris

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.

Gender: All

Minimum Age: N/A

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Sonata Jodele, MD Principal Investigator Children's Hospital Medical Center, Cincinnati
Overall Contact

Last Name: Stephanie L Edwards, BSN, RN

Phone: 513-636-9292

Email: [email protected]

Location
Facility: Status: Investigator:
Children's Hospital Los Angeles (CHLA) | Los Angeles, California, 90027, United States Recruiting Paibel Aguayo-Hiraldo, MD Principal Investigator
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio, 45229, United States Recruiting Stephanie Edwards, BSN, RN 513-636-9292 [email protected] Sonata Jodele, MD Principal Investigator
Children's Hospital of Philadelphia (CHOP) | Philadelphia, Pennsylvania, 19104, United States Recruiting Jason Freedman, MD Principal Investigator
Location Countries

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Eculizumab

Type: Experimental

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

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov