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

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 malingnant 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: Immune-Related Adverse Events
• Intervention / Treatment: Drug: Rituximab (RTX)

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Inge Marie Svane, Professor, MD, PhD; Phone Number: 004538683868; Email: inge.marie.svane@regionh.dk
• Study Contact Backup: Name: Frederikke Strauss Hansen, MD, PhD-student; Phone Number: 004538683868; Email: frederikke.strauss.hansen@regionh.dk

Study Locations

• Denmark
  • Herlev
    • Herlev, Herlev, Denmark, 2730
      • National Center for Cancer Immune Therapy, Department of Oncology, Herlev Hospital
      • Contact: Frederikke Strauss Hansen, MD, PhD-student; Phone Number: 004538683868; Email: frederikke.strauss.hansen@regionh.dk
      • Contact: Email: frederikke.strauss.hansen@regionh.dk

Participation Criteria

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, creamor suppository, male sterilization, or true abstinence throughout study and for a minimum of 3 months after study drug therapy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

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	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	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	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	Assessment of rituximab efficacy measured as cumulative dose and peak dose of corticosteroids.	Until 6 months post treatment
Second- or third-line immunosuppressants	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	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

• Sponsor: Inge Marie Svane

Study record dates

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 10, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Rituximab; Malignant melanoma; Immune-related adverse event; Checkpoint inhibitors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab
• 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