Immune-Related Adverse Events
Conditions
Keywords
Rituximab, Immunotherapy, Checkpoint inhibitors, Malignant melanoma, Immune-related adverse event
Brief summary
The goal of this clinical trial is to investigate the safety of rituximab for management of immune-related adverse events in malignant melanoma patients. The main questions it aims to answer are: * Is rituximab safe for management of immune-related adverse events in malignant melanoma patients? * Does rituximab provide indications of clinical benefit in the management of immune-related adverse events compared with corticosteroid treatment alone? Participants will: * Receive a single dose of 100 mg rituximab IV * Have regular follow-up consultations for 6 months following rituximab infusion * Follow a simultaneous corticosteroid tapering plan
Interventions
DRUGRituximab (RTX)
A single ultra-low dose rituximab (100 mg) infusion for patients with immune-related adverse events
Sponsors
Inge Marie Svane
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed malignant melanoma diagnosis * Treatment with immune checkpoint inhibitors (anti-PD1, anti-PDL1, anti-LAG3 and/or anti-CTLA4) due to melanoma within 3 months * Any irAEs grade 2-4 according to CTCAE v. 6.0 * Negative pregnancy test (serum hCG) in women of childbearing potential * Age ≥ 18 years * Ability to provide written and oral consent * The patient is able to understand and read Danish
Exclusion criteria
* Any ongoing infectious disease * Neutropenia (\<1.5 x10\^9/L) and/or thrombocytopenia (\<75 x10\^9/L) * Known hypersensitivity towards the active substance rituximab or any of the excipients * History of cardiovascular disease including severe heart failure NYHA grade 3-4, unstable angina pectoris, atrial fibrillation, atrial flutter, and myocardial infarction * Any major wounds * Low baseline IgG (\<6 g/L) * Positive hepatitis B virus, hepatitis C virus, HIV, or tuberculosis screening * Concomitant immunosuppressive medication except prednisolone * Concomitant chemotherapy or other antineoplastic therapy (except checkpoint inhibitor therapy) within 30 days prior to inclusion * Females of childbearing potential or males of reproductive potential who are not willing to use an effective method of contraception, such as oral, injected, or implanted hormonal methods of contraception, intrauterine device or intrauterine system, condom in combination with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam, gel, film, cream or suppository, male sterilization, or true abstinence throughout study and for a minimum of 3 months after study drug therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of rituximab-related adverse events graded according to CTCAE v. 6.0 | Until 6 months post treatment | Safety of rituximab is evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) v. 6.0 and include the incidence and severity of rituximab-related adverse events until 6 months post treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune-related adverse event management response | Until 6 months post treatment | The immune-related adverse events management response, defined as number of days until symptom control (corresponding to CTCAE grade 0-1 of the immune-related adverse event) |
| Corticosteroid dependency | Until 6 months post treatment | Corticosteroid dependency in rituximab treated patients measured as the number of days on corticosteroids following rituximab infusion. |
| Dose of corticosteroids | Until 6 months post treatment | Assessment of rituximab efficacy measured as cumulative dose and peak dose of corticosteroids. |
| Second- or third-line immunosuppressants | Until 6 months post treatment | Assessment of rituximab efficacy measured as the proportion of patients requiring second- or third-line immunosuppressive therapy after rituximab |
Countries
Denmark
Contacts
CONTACTInge Marie Svane, Professor, MD, PhD
CONTACTFrederikke Strauss Hansen, MD, PhD-student
Outcome results
None listed