Study of Rituximab or Tocilizumab for Patients With Steroid-Dependent Immune-Related Adverse Events (irAEs)

NCT04375228 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAS9173
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to examine how effective rituximab or tocilizumab are in treating side effects for people who are receiving immunotherapy treatment requiring prolonged steroid use. Immune-related side effects are caused by the activation of the immune system. Because rituximab and tocilizumab have been shown to effectively in treating other diseased that involve immune system activation, this study seeks to evaluate how effective they will be in treating immune-related side effects in people receiving immunotherapy treatment for cancer.

Conditions

Advanced Solid Tumor; Immune-related Adverse Events

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants to Discontinue Steroid Treatment After Rituximab

  The percentage of participants able to discontinue steroid treatment within 4 weeks after the last dose of Rituximab.

  Up to 8 weeks

• Percentage of Participants to Discontinue Steroid Treatment After Tocilizumab

  The percentage of participants able to discontinue steroid treatment within 4 weeks after the last dose of Tocilizumab.

  Up to 12 weeks

Secondary Outcomes (2)

• Number of Participants with a Change in CTCAE (v5.0) Grade

  Up to 24 weeks

• The Number Steroid-Dependent Immune-Related Adverse Events

  Up to 24 weeks

Study Arms (2)

Rituximab

EXPERIMENTAL

Patients with histologically confirmed advanced (metastatic or unresectable) solid tumors that have documented irAEs will receive Rituximab.

Drug: Rituximab

Tocilizumab

EXPERIMENTAL

Patients with histologically confirmed advanced (metastatic or unresectable) solid tumors that have documented irAEs will receive Tocilizumab.

Drug: Tocilizumab

Interventions

Rituximab DRUG

375mg/m\^2 IV weekly for 4 doses

Also known as: RITUXAN

Rituximab

Tocilizumab DRUG

4mg/kg IV once a month for up to 2 doses

Also known as: ACTEMRA

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed advanced (metastatic or unresectable) solid tumors that develop irAEs secondary to treatment with immune checkpoint inhibitors. Diagnostic evaluation of irAEs must include agreement between medical oncologist and disease-specific subspecialist (e.g. rheumatologist, dermatologist) on therapeutic rationale for either rituximab or tocilizumab-based therapy or if evidence-based indications exist as summarized below: Dermatologic (bullous pemphigoid, pemphigus vulgaris) - Rituximab. Neurologic (autoimmune encephalitis) - Rituximab. Hematologic (immune thrombocytopenia, autoimmune hemolytic anemia) -Rituximab. Rheumatologic (rheumatoid arthritis, psoriatic arthritis) -Rituximab/Tocilizumab.
• Renal (autoimmune nephritis) - Rituximab. Pulmonary (pneumonitis) - Tocilizumab. Cardiac (autoimmune myocarditis) - Tocilizumab
• Steroid-dependent, defined as inability to wean less than 10mg of prednisone (or equivalent) after 6 weeks of therapy; patients who develop intolerance to steroids (e.g.
• myopathy or hyperglycemia) may be enrolled earlier than 6 weeks at the discretion of the treating physician and/or the principal investigator.
• Be willing and able to provide written informed consent/assent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Female subject of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential should be willing to use contraception, or abstain from heterosexual activity for the course of the study and through 12 months after last dose of rituximab or 3 months after last dose of tocilizumab. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• Males must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months after last dose of rituximab, 180 days even if he has undergone a successful vasectomy
• Vaccinations must be completed 4 weeks prior to the first treatment with rituximab or must not be taken at least 6 months after the last dose of chemotherapy. Non-live vaccines may be given during rituximab treatment; however, patients may experience reduced response rates. The safety of live vaccines has not been studied during cancer treatment and their use is not recommended unless otherwise advised by the oncologist.
• Subject must be vaccinated with the pneumococcal vaccine at least 4 weeks prior to initiation of therapy, unless subject was vaccinated within 5 years of study entry. If vaccination occurred greater than 5 years prior to study entry, the subject must be revaccinated at least 4 weeks prior to initiation of therapy
• Have adequate organ and marrow function as defined below: Absolute Neutrophil Count ≥1,000/microliters Platelets ≥100,000 Hemoglobin ≥ 7.0g/dL (without transfusion in past 2 weeks) Note: Patients with cytopenias (e.g immune thrombocytopenia, autoimmune hemolytic anemia) clinically consistent with irAE will be eligible at the discretion of principal investigator. Patients with hematological values below those stated will not receive Tocilizumab aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT)(SGPT) ≤2 × institutional upper limit of normal Creatinine clearance of ≥ 30 mL/min. Creatinine clearance (CrCl) should be calculated at screening using the Cockcroft-Gault formula.
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

You may not qualify if:

• Current participation in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
• Diagnosis of immunodeficiency or is receiving systemic immunosuppressive therapy other than steroids prior to the first dose of trial treatment
• Treatment with a non-biologic immunosuppressive or immune-modulating drug (e.g. methotrexate, azathioprine, mycophenolate, cyclosporine, hydroxychloroquine, penicillamine) within 4 weeks prior to treatment. Note: Patients who previously received treatment with either rituximab or tocilizumab may receive treatment with the alternative agent after discussion with the treating physician and/or the principal investigator.
• Treatment with other immune-modulating biologic agents within 4 weeks prior to treatment initiation.
• History of anaphylaxis or immunoglobulin E-mediated hypersensitivity to murine proteins or any component of rituximab or tocilizumab History of allergic reactions attributed to compounds of similar chemical or biologic composition to either rituximab or tocilizumab.
• History of human immunodeficiency virus (HIV) infection or other immunodeficiency.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• History of chronic viral hepatitis, alcoholic or metabolic liver disease. Carriers of hepatitis B and patients with a history of hepatitis B infection or positive serology are excluded except in situations where the potential benefit is determined to justify the risk of possible hepatitis B reactivation, which can be fatal. Patients with positive serology should have viral DNA levels checked and a gastrointestinal consultation obtained. If treated with rituximab, such patients should be closely monitored for clinical and laboratory signs of active hepatitis B virus infection and for signs of hepatitis throughout their study participation.
• Central nervous system (CNS) metastases, with the following exception:
• Subjects who have previously-treated CNS metastases, are asymptomatic, and have no requirement for steroids in the management of CNS disease (steroids for irAEs are allowed) at least 14 days prior to first dose of study drug. Note: Subjects with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Transplanted organs (except corneas with transplant performed \>3 months prior to screening)
• Active infection, including opportunistic infections, requiring systemic therapy within the past 2 weeks.
• A deep space infection within the past 2 years (including, but not limited to meningitis, epiglottitis, endocarditis, septic arthritis, fasciitis, abdominal or pleural abscess, or osteomyelitis).

Sponsors & Collaborators

• Columbia University: lead
• Genentech, Inc.: collaborator

Study Sites (3)

Johns Hopkins

Baltimore, Maryland, 21224, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10022, United States

Location

Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

MeSH Terms

Interventions

Rituximab; tocilizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Brian Henick, MD

  Assistant Professor of Medicine in the Division of Hematology and Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Model Details: Participants will be assigned either rituximab or tocilizumab based on clinical rationale and consensus recommendation by investigators.

Study Record Dates

• First Submitted: May 1, 2020
• First Posted: May 5, 2020
• Study Start: September 25, 2020
• Primary Completion: May 14, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)