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

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.

Study Overview

• Status: Completed
• Conditions: Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome; Multiple Organ Dysfunction Syndrome
• Intervention / Treatment: Drug: Eculizumab

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 Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles (CHLA)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia (CHOP)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eculizumab; All patients will receive eculizumab based on their weight for 24 weeks.	Drug: Eculizumab; 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.; Other Names: Soliris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Survival at 6 months after the date of TMA diagnosis	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	1 year
Non-relapse Mortality	Non-relapse mortality descriptively compared with historical controls at 1 year	1 year

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Sonata Jodele, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2018
• Primary Completion (Actual): April 4, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: May 4, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cell Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Hematologic Diseases; Shock; Anemia; Thrombocytopenia; Blood Platelet Disorders; Anemia, Hemolytic; Uremia; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Syndrome; Vascular Diseases; Thrombotic Microangiopathies; Multiple Organ Failure; Azotemia; Hemolysis; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab
• Other Study ID Numbers: 2018-7119C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No