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

• ClinicalTrials.gov Identifier: NCT03518203
• Recruitment Status: Active, not recruiting
• First Posted: May 8, 2018
• Last Update Posted: December 14, 2021
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

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.

Condition or disease	Intervention/treatment	Phase
Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome; Multiple Organ Dysfunction Syndrome	Drug: Eculizumab	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 3, 2018
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

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 Name: Soliris

Outcome Measures

Primary Outcome Measures :

1. Survival [ Time Frame: 6 months ]
   Survival at 6 months after the date of TMA diagnosis

Secondary Outcome Measures :

1. Incidence of organ dysfunction [ Time Frame: 6 months ]
   Incidence of organ dysfunction at 6 months after TMA diagnosis
2. Incidence of organ dysfunction [ Time Frame: 1 year ]
   Incidence of organ dysfunction at 1 year after TMA diagnosis
3. Time to resolution of organ dysfunction [ Time Frame: 1 year ]
   Timing of resolution of organ dysfunction in the first year after therapy. Resolution of organ dysfunction is assessed based on protocol-defined multiple organ dysfunction syndrome criteria.
4. Non-relapse mortality [ Time Frame: 1 year ]
   Non-relapse mortality compared with historical controls at 1 year

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Children's Hospital Los Angeles (CHLA)

Los Angeles, California, United States, 90027

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, Pennsylvania

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Investigators

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

More Information

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT03518203
• Other Study ID Numbers: 2018-7119C
• First Posted: May 8, 2018
• Last Update Posted: December 14, 2021
• Last Verified: December 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Children's Hospital Medical Center, Cincinnati:

Hematopoietic Stem Cell Transplant

Additional relevant MeSH terms:

Azotemia; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Vascular Diseases; Thrombotic Microangiopathies; Syndrome; Hemolysis; Multiple Organ Failure; Disease; Pathologic Processes; Uremia; Kidney Diseases; Urologic Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Thrombocytopenia; Blood Platelet Disorders; Cardiovascular Diseases; Shock; Eculizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs