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

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ClinicalTrials.gov Identifier: NCT03518203
Recruitment Status : Active, not recruiting
First Posted : May 8, 2018
Last Update Posted : December 14, 2021
Sponsor:
Information provided by (Responsible Party):
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.

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.

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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


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




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



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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03518203


Locations
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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
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Principal Investigator: Sonata Jodele, MD Children's Hospital Medical Center, Cincinnati
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03518203    
Other Study ID Numbers: 2018-7119C
First Posted: May 8, 2018    Key Record Dates
Last Update Posted: December 14, 2021
Last Verified: December 2021

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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:
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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