Study of Patients With Thrombotic Microangiopathy Associated With Mitomycin C, Treated or Not With Eculizumab

NCT06098378 | Unknown

• 1 other identifier: 8957
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Thrombotic microangiopathies (TMA) are defined as a triad combining mechanical hemolytic anemia, peripheral thrombocytopenia and ischemic organ damage. Mitomycin C is an alkylating agent used as chemotherapy in adenocarcinomas of the breast, lung, pancreas, rectum and anal carcinoma. Mitomycin-C-induced TMA (m-TMA) is a potentially serious complication of chemotherapy: its estimated incidence ranges from 4 to 15% and its mortality exceeds 70%, with an estimated median survival of 2 months. This can also be responsible for kidney failure, sometimes requiring hemodialysis. The time to onset of m-TMA varies from one week to 15 months after the last infusion and is believed to depend on the cumulative dose of mitomycin C. Eculizumab is a monoclonal antibody that binds to complement protein C5, blocking activation of the terminal complement pathway and formation of the membrane attack complex. This therapy has significantly changed the prognosis of patients with atypical hemolytic uremic syndrome (HUS), a disease in which complement activation plays a central role in TMA. Recently, a retrospective study suggested efficacy of eculizumab in TMA induced by gemcitabine, another chemotherapy, with normalization of platelets and LDH in 83% of patients, and partial or complete renal recovery in 67% and 17% of patients. These results provided arguments in favor of a potential benefit of complement-targeted therapies in TMA induced by certain chemotherapies. However, data on eculizumab in m-TMA remain extremely limited to date. The objective of this study is to describe the clinical, biological and histological presentation of patients with m-TMA and their evolution after treatment with or without eculizumab.

Conditions

Thrombotic Microangiopathies

Keywords

Thrombotic Microangiopathies; Mitomycin C; Mitomycin-C-induced TMA; m-TMA; Eculizumab; Hemolytic uremic syndrome

Outcome Measures

Primary Outcomes (1)

• Overall and renal survival after the m-TMA episode

  Files analysed retrospectively from January 01, 1990 to December 31, 2023 will be examined

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients (\>=18 years) having developed a picture of thrombotic microangiopathy attributed to mitomycin C between 01/01/1990 and 12/31/2023

You may qualify if:

• Adult patients (\>=18 years)
• Having received treatment with mitomycin C (regardless of the method of administration and indication) between 01/01/1990 and 12/31/2023
• and having developed a picture of thrombotic microangiopathy attributed to mitomycin C:
• biological: defined as: thrombocytopenia \<150G/L and mechanical hemolytic anemia (at least 3 out of 4 criteria: hemoglobin \< 12g/dL, presence of schistocytes in blood smear, LDH \> 1N, collapsed haptoglobin (\< lower limit of the limit of laboratory normal)
• or renal: pathological diagnosis of thrombotic microangiopathy on renal biopsy
• having received or not treatment for the episode of microangiopathy, including or not complement inhibitors (Eculizumab).
• Subject not opposing, after information, the reuse of their data for the purposes of this research

You may not qualify if:

• Subject having expressed opposition to participating in the study
• Test for positive Shiga toxin
• ADAMST13 activity \<10%
• Thrombotic microangiopathy attributed to metastatic cancer (infiltration of bone marrow or circulating erythroblasts)
• Impossibility of providing the subject with informed information (difficulties in understanding the subject, etc.)
• Subject under judicial protection
• Subject under guardianship or curatorship

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Service de Néphrologie, Dialyse et Transplantation - CHU de Strasbourg - France

Strasbourg, 67091, France

RECRUITING

MeSH Terms

Conditions

Thrombotic Microangiopathies; Hemolytic-Uremic Syndrome

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia

Central Study Contacts

Anna DUVAL, MD

CONTACT

33 3 69 55 05 11; anna.duval@chru-strasbourg.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 24, 2023
• Study Start: June 7, 2023
• Primary Completion: June 1, 2025
• Study Completion: June 7, 2025
• Last Updated: October 24, 2023

Record last verified: 2023-10

Locations

FR (1)