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

NCT03518203 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2018-7119C
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

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.

Conditions

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

Keywords

Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Survival

  Survival at 6 months after the date of TMA diagnosis

  6 months

Secondary Outcomes (3)

• Number of Participants With Organ Dysfunction

  6 months

• Number of Participants With Organ Dysfunction

  1 year

• Non-relapse Mortality

  1 year

Study Arms (1)

Eculizumab

EXPERIMENTAL

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

Drug: Eculizumab

Interventions

Eculizumab DRUG

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.

Also known as: Soliris

Eculizumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (3)

Children's Hospital Los Angeles (CHLA)

Los Angeles, California, 90027, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Jodele S, Dandoy CE, Aguayo-Hiraldo P, Lane A, Teusink-Cross A, Sabulski A, Mizuno K, Laskin BL, Freedman J, Davies SM. A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation-associated TMA. Blood. 2024 Mar 21;143(12):1112-1123. doi: 10.1182/blood.2023022526.

  PMID: 37946262 DERIVED

MeSH Terms

Conditions

Thrombotic Microangiopathies; Atypical Hemolytic Uremic Syndrome; Multiple Organ Failure

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Hemolytic-Uremic Syndrome; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Shock; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Sonata Jodele, MD
• Organization: Cincinnati Children's Hospital Medical Center

Sonata.Jodele@cchmc.org

(513) 636-5917

Study Officials

• Sonata Jodele, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: May 8, 2018
• Study Start: August 3, 2018
• Primary Completion: April 4, 2022
• Study Completion: June 1, 2022
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-08

Locations

US (3)