Rituximab for Treatment of Checkpoint Inhibitor Induced Immune-related Adverse Events (RiTOX)

July 20, 2026 updated by: Inge Marie Svane

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituximab
Drug: Rituximab (RTX)
A single ultra-low dose rituximab (100 mg) infusion for patients with immune-related adverse events

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of rituximab-related adverse events graded according to CTCAE v. 6.0
Time Frame: 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.
Until 6 months post treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune-related adverse event management response
Time Frame: 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)
Until 6 months post treatment
Corticosteroid dependency
Time Frame: Until 6 months post treatment
Corticosteroid dependency in rituximab treated patients measured as the number of days on corticosteroids following rituximab infusion.
Until 6 months post treatment
Dose of corticosteroids
Time Frame: Until 6 months post treatment
Assessment of rituximab efficacy measured as cumulative dose and peak dose of corticosteroids.
Until 6 months post treatment
Second- or third-line immunosuppressants
Time Frame: Until 6 months post treatment
Assessment of rituximab efficacy measured as the proportion of patients requiring second- or third-line immunosuppressive therapy after rituximab
Until 6 months post treatment

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in circulating B cells
Time Frame: Until 16 weeks post treatment
Changes in circulating B cells/B cell depletion will be evaluated by assessing changes in CD19+ and/or CD20+ B cell counts from baseline to 16 weeks post treatment.
Until 16 weeks post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inge Marie Svane

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

July 1, 2026

First Submitted That Met QC Criteria

July 1, 2026

First Posted (Actual)

July 10, 2026

Study Record Updates

Last Update Posted (Actual)

July 22, 2026

Last Update Submitted That Met QC Criteria

July 20, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AA2603
  • 2026-525728-18-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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