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. There will be no limitation based on gender and upper limit age.
Conditions
Interventions
Trade Name: ORENCIA 250 mg powder for concentrate for solution for infusion
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: ABATACEPT
CAS Number: 332348-12-6
Sponsors
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years old 2. Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer 3. Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations 4. Severe or corticosteroid-resistant ICI-myocarditis: - Severe ICI-myocarditis is defined either 1/ by the appearance of an alteration of the LVEF=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
Exclusion criteria: 1. Untreated 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 (RIPH1 only) 8. People under legal protection measure (tutorship, curatorship or safeguard measures)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to find the lowest dose required to achieve a circulating monocytes CD86RO=80% within the first week of treatment and sustainably over three weeks;Secondary Objective: - To evaluate the immunological, myocardial and muscular pharmacodynamic effects of 3 different doses of abatacept in the initial phase (first 21 days) of ICI-myocarditis treatment. - To assess the pharmacokinetic properties of abatacept used in ICI-myocarditis - Pharmacokinetic / pharmacodynamic (PK-PD) modeling of abatacept in ICI-myocarditis - To assess the safety of these different doses (pro-tumorigenicity, infections). - To evaluate long-term effects of abatacept treatment in ICI-myocarditis over months, up to one year;Primary end point(s): Proportion of patients with CD86RO saturation =80% within the first week of treatment and sustainably over three weeks after randomization. CD86RO will be assessed versus baseline levels (one hour before abatacept administration) at the following timepoints: once 1 to 3 hours after, and once 24 to 72 hours after the first, 2nd and 3rd abatacept dose and a last one at Day 21 after the first administration of abatacept. A patient will be considered with a CD86RO saturation =80% within the first week of treatment if at least three CD86RO assessments are over 80% until Day 21 after the first administration of abatacept.;Timepoint(s) of evaluation of this end point: D21 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Quantification of proxies reflecting the resolution of systemic immune activation: % of regulator T-cells CTLA4+, levels of pro and anti-inflammatory cytokines, C-reactive protein levels, % of circulating monocytes expressing PDL1, % of circulating T-cells expressing PD1. There will be assessed versus baseline levels (one hour before abatacept treatment) and at the following timepoints: once 1 to 3 hours after, and once 24 to 72 hours after the first, 2nd and 3rd abatacept dose, then every ten days up to day 90, and then every three months up to a year of follow-up. In case of additional doses of abatacept, these proxies will also be additionally measured one hour before and one to three hours after each dose of abatacept. - Quantification of the corticosteroid decrease kinetics (total cumulative dose) and the proportion of patients for whom it was necessary to add other immunosuppressants in addition to glucocorticoids to control the disease during the first 21 days and then 90days of the disease : Area under the curve of troponin-T levels; incidence of heart failure (defined as left-ventricular drop below 50%); and incidence of life-threatening cardiac arrhythmias (defined a sustained =30 seconds ventricular tachycardia episode, ventricular fibrillation, cardiac arrest, sinus arrest >4 seconds and complete atrio-ventricular block). - Quantification of proxies reflecting the resolution of myocarditis: troponin-T and -I, CK, NT-proBNP, left ventricular ejection fraction by echocardiography, cardiac inflammation and myocardial edema quantification evaluated by cardiac MRI, arrhythmias and ventricular conductive disorders quantified on electrocardiographic Holter acquisitions; and humoral autoimmunity against the myocardium or the muscles (anti-troponin I and T, anti-myosin, anti-musK, anti-acetylcholine receptor antibodies). The imaging modalities (MRI, echocardiography) will be assessed at least once as soon as possible after admission, | — |
Countries
France
Contacts
Public ContactSophie COURTIAL-DESTEMBERT
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed