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

Primary Purpose

Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Dysfunction Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eculizumab
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thrombotic Microangiopathies focused on measuring Hematopoietic Stem Cell Transplant

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Children's Hospital Los Angeles (CHLA)
  • Cincinnati Children's Hospital Medical Center
  • Children's Hospital of Philadelphia (CHOP)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eculizumab

Arm Description

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

Outcomes

Primary Outcome Measures

Survival
Survival at 6 months after the date of TMA diagnosis

Secondary Outcome Measures

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

Full Information

First Posted
March 5, 2018
Last Updated
September 20, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT03518203
Brief Title
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 3, 2018 (Actual)
Primary Completion Date
April 4, 2022 (Actual)
Study Completion Date
June 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Microangiopathies, Atypical Hemolytic Uremic Syndrome, Multiple Organ Dysfunction Syndrome
Keywords
Hematopoietic Stem Cell Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eculizumab
Arm Type
Experimental
Arm Description
All patients will receive eculizumab based on their weight for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Eculizumab
Other Intervention Name(s)
Soliris
Intervention 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.
Primary Outcome Measure Information:
Title
Survival
Description
Survival at 6 months after the date of TMA diagnosis
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of Participants With Organ Dysfunction
Description
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
Title
Number of Participants With Organ Dysfunction
Description
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
Title
Non-relapse Mortality
Description
Non-relapse mortality descriptively compared with historical controls at 1 year
Time Frame
1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sonata Jodele, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital Los Angeles (CHLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Children's Hospital of Philadelphia (CHOP)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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