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ACTIVE NOT RECRUITING

NCT05195645

PHASE2

AbataCept for the Treatment of Immune-cHeckpoint Inhibitors Induced mYocarditiS

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

Summary

Immune-checkpoint-inhibitors (ICI) have revolutionized treatment for about 20 cancer types. They unleash anti-tumor immune responses. Unfortunately, in 0.36-1.23% of patients, this activation can also lead to lethal immune-related adverse events (irAEs) that can affect any organ. Among those irAEs, ICI-induced myocarditis was the most frequently fatal with death rate reaching 50% in a large case-series of over 100 patients. This study is a dose-finding Phase II trial where 3 abatacept IV regimen (A-10 mg/kg; B-20 mg/kg and C-25 mg/kg at Day0, Day5+/-2, Day14+/-2) will be tested aiming at reaching promptly (after the first dose) and sustainably a CD86RO≥80% during the first 3 weeks of ICI-myocarditis management. The main objective is to find the lowest dose required to achieve a circulating monocytes CD86RO≥80% within the first week of treatment and sustainably over three weeks. The target population is all adult patients with cancer (all cancer types) treated by immune checkpoint inhibitors (anti-PD1, anti-PDL1, anti-CTLA4 monotherapies or combination) and presenting drug-induced myocarditis.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2022-10-04

Completion Date

2025-09-15

Last Updated

2024-12-13

Healthy Volunteers

Conditions

Myocarditis

Interventions

DRUG

Abatacept 250 MG

Abatacept will be administered by intravenous injection over 1h15 to 2h30 on D1, D5+/-2 and D14+/-2 at 10mg/kg (arm A), or 20mg/kg (arm B) or 25mg/kg (arm C) depending on the randomization (max 3 000 mg per administration). Starting Day 21 (after evaluation of the primary outcome), other injection of abatacept may be given (D22 at D90) with dosage (10 or 20mg/kg max) decided by the treating physician (max 2 500 mg per administration) as a function of the relapse or not of the ICI myocarditis after immunosuppressant therapeutics tapering. After day 21, the administrations will be carried out in open but the blind administration 1 to 3 (D1 to D21) will be kept.

Inclusion Criteria: 1. Age ≥ 18 years old 2. Weight ≥ 40 kg and ≤ 125 kg 3. Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer (even those in which ICI is not currently approved by regulatory) 4. Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations (e.g27, to be updated with any new recommendations to be published) 5. Severe or corticosteroid-resistant ICI-myocarditis: * Severe ICI-myocarditis is defined either 1/ by the appearance of an alteration of the LVEF\<50% or a wall motion kinetics abnormality, or 2/ by the appearance of ventricular tachycardias or high-grade conductive disorders (atrioventricular block grade 2 or 3) or 3/ by the association with myasthenia gravis-like-syndrome (diplopia, ptosis, diaphragmatic dysfunction, dysarthria, dysphonia, dysphagia) or 4/ by troponin-T levels above 32 times the upper limit of the normal (a population at very high-risk \~75% of major cardiomuscular events in the month following initial presentation, cf. Circulation. 2023 Aug 8;148(6):473-486). * Corticosteroid-resistant ICI-myocarditis is defined by the absence of decrease in troponin levels or the appearance/persistence of severity criteria despite receiving prednisone dose ≥0.5 mg/kg/day for ≥2 days. 6. Signature of informed consent before any trial procedure from the patient or legal representative or the close relative 7. Patients covered by social security regimen (excepting AME) 8. Withhold of ICI Exclusion Criteria: 1. Untreated and/or uncontrolled bacterial, fungal, or viral infection 2. Pregnancy, breast-feeding or planning to become pregnant during the study period 3. For women of childbearing age, lack of effective contraception throughout the duration of participation in the study 4. Being treated with abatacept or belatacept within 3 months prior to inclusion 5. Known hypersensitivity to abatacept or belatacept 6. Being treated with anti-thymoglobulin, or alemtuzumab within 6 weeks of the first scheduled dose of abatacept 7. Patient participating to another interventional study (RIPH 1 only) 8. People under legal protection measure (tutorship, curatorship or safeguard measures)

Locations (1)

Hôpital Pitié Salpêtrière

Paris, France