Eculizumab to Treat Thrombotic Microangiopathy/Atypical Hemolytic Uremic Syndrome -Associated Multiple Organ Dysfunction Syndrome in Hematopoietic Stem Cell Transplant Recipients
Study Details
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 |
---|---|---|
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
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 Names:
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Outcome Measures
Primary Outcome Measures
- Survival [6 months]
Survival at 6 months after the date of TMA diagnosis
Secondary Outcome Measures
- Incidence of organ dysfunction [6 months]
Incidence of organ dysfunction at 6 months after TMA diagnosis
- Incidence of organ dysfunction [1 year]
Incidence of organ dysfunction at 1 year after TMA diagnosis
- Time to resolution of organ dysfunction [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.
- Non-relapse mortality [1 year]
Non-relapse mortality compared with historical controls at 1 year
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients of any age undergoing allogeneic or autologous HCT
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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.
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Minimum weight of ≥ 5kg.
Exclusion Criteria:
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Known hypersensitivity to any constituent of the study medication.
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Subjects with unresolved serious Neisseria meningitides infection or progressive severe infection.
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Patients with diagnosis of TTP as defined by ADAMST13 activity test <10%.
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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
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Children's Hospital Los Angeles (CHLA) | Los Angeles | California | United States | 90027 |
2 | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | United States | 45229 |
3 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2018-7119C