Rituximab or Tocilizumab for Immune-Related Side Effects

Recruiting at 2 trial locations

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Columbia University

Must be taking: Steroids

Must not be taking: Non-biologic immunosuppressives

Disqualifiers: Immunodeficiency, HIV, Hepatitis, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking non-biologic immunosuppressive or immune-modulating drugs (like methotrexate or azathioprine) and other immune-modulating biologic agents at least 4 weeks before starting the trial treatment. If you are on steroids, you may continue them as they are part of the trial's treatment plan.

What data supports the effectiveness of the drug Tocilizumab for immune-related side effects?

Tocilizumab has been shown to be effective in treating rheumatoid arthritis, a condition where the immune system attacks the joints, by reducing disease activity and improving quality of life. This suggests it may help manage immune-related side effects by modulating the immune response. ^{1 2 3 4 5}

How does rituximab differ from other drugs for immune-related side effects?

Rituximab is unique because it specifically targets CD20 molecules on B-cells, which helps deplete these cells and regulate the immune system. This mechanism is different from other treatments that may not target B-cells directly. However, it can cause infusion-related reactions and other side effects, which are important to consider. ^{6 7 8 9 10}

Research Team

Brian Henick, MD

Principal Investigator

Assistant Professor of Medicine in the Division of Hematology and Oncology

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors who have immune-related side effects from immunotherapy and can't reduce their steroid use below a certain level. They must be able to consent, not be pregnant or breastfeeding, agree to contraception, have adequate organ function, and not have any conditions that would interfere with the study.

Inclusion Criteria

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.

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.

Exclusion Criteria

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

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Rituximab or Tocilizumab to manage steroid-dependent immune-related adverse events

8-12 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up visits to assess discontinuation of steroid treatment

Treatment Details

Interventions

• Rituximab
• Tocilizumab

Trial Overview The study tests Rituximab or Tocilizumab's effectiveness in treating immune-related adverse events in cancer patients on prolonged steroids due to immunotherapy. It aims to see if these drugs can manage side effects caused by an activated immune system.

Participant Groups

Group I: Tocilizumab Experimental Treatment 1 Intervention

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

Group II: Rituximab Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

About 30% of the 1012 patients studied received rituximab off-label for conditions like rheumatoid arthritis, indicating its widespread use beyond approved indications.

Most patients were unaware of the risk of progressive multifocal leukoencephalopathy (PML) associated with rituximab, with only 32.8% receiving the Patient Alert Card (PAC) designed to inform them about this risk, although those who did receive the PAC had better awareness of PML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card. Sarsour, K., Beckley-Kartey, S., Melega, S., et al.[2020]

Tocilizumab, an anti-IL-6 receptor monoclonal antibody, has shown significant clinical efficacy in treating moderately to severely active rheumatoid arthritis, achieving disease remission in 30% of patients who did not respond to anti-TNF therapy after 24 weeks of treatment.

While tocilizumab is generally well-tolerated, common side effects include upper respiratory infections and mild liver enzyme increases, with serious risks such as infections and gastrointestinal perforations, leading to its approval in over 70 countries for rheumatoid arthritis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of rheumatoid arthritis. Tanaka, T., Ogata, A., Narazaki, M.[2016]

Tocilizumab is an effective treatment for adults with moderate to severe rheumatoid arthritis (RA), showing beneficial effects on disease symptoms and quality of life, based on several large clinical trials and studies.

Long-term use of tocilizumab (up to 9 years) is generally well tolerated, with infections being the most common side effect, and it has been shown to be more effective than adalimumab in patients who cannot continue methotrexate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. Dhillon, S.[2022]

Tocilizumab is an effective treatment option for rheumatoid arthritis in patients who have not responded to other therapies, but it is not more effective than rituximab in cases of multiple treatment failures, based on clinical evaluations of four placebo-controlled trials.

While tocilizumab offers convenience with intravenous administration every four weeks, it carries significant risks of serious infections and other adverse effects, and its long-term safety profile, particularly regarding cancer risk, remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: new drug. Rheumatoid arthritis: another 'mab', no therapeutic advantage. [2016]

Tocilizumab, an IL-6 receptor antagonist, is effective and well tolerated for treating moderate to severe rheumatoid arthritis, showing better results than placebo and other DMARDs in reducing disease activity and improving quality of life.

It is particularly beneficial for patients who have not responded to anti-TNF therapies, making it a valuable option for those with long-standing rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the management of rheumatoid arthritis. Oldfield, V., Dhillon, S., Plosker, GL.[2021]

Rituximab, a monoclonal antibody used for treating certain cancers and autoimmune diseases, is generally well tolerated but can cause serious side effects, including rare but life-threatening cardiovascular events like myocardial infarction.

A case study of a 58-year-old man revealed that he experienced a ST-elevation myocardial infarction during rituximab treatment, highlighting the need for careful screening for ischemic heart disease in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. Sharif, K., Watad, A., Bragazzi, NL., et al.[2022]

In a study of 70 multiple sclerosis patients receiving rituximab, 25.7% experienced infusion-associated reactions, primarily mild to moderate, mostly during the first infusion.

Premedication with corticosteroids significantly reduces the incidence of these reactions, and effective management strategies include using antihistamines and adjusting the infusion rate if reactions occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: a retrospective analysis of patients treated at a US centre. Brown, BA., Torabi, M.[2021]

In a case series of 3 patients treated with rituximab for connective tissue diseases, all developed moderate to severe tendonitis after the second infusion, with confirmation through MRI in 2 cases.

The tendonitis symptoms resolved within 3-4 months, but one patient experienced progressive tendon damage leading to rupture, indicating a potential cause-effect relationship that requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tendonitis and Tendon Rupture After Treatment With Rituximab: A Case Series. Alqahtani, A., Sabha, M., Abdelfattah, T., et al.[2022]

Rituximab, an anti-CD20 monoclonal antibody used for treating cutaneous lymphoid malignancies, has been associated with rare side effects, including vasculitis.

This report details a case of a 38-year-old Korean man who developed cutaneous vasculitis just one day after receiving rituximab, highlighting the need for awareness of this potential adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab-induced vasculitis: A case report and review of the medical published work. Kim, MJ., Kim, HO., Kim, HY., et al.[2020]

Rituximab effectively targets and depletes CD20-positive B-cells, making it useful for treating various conditions, including B-cell lymphoma and several neurological disorders, even in difficult cases.

While it can lead to significant side effects such as infusion reactions and long-term risks like reactivation of Hepatitis B and severe infections, modifications to the antibody have been made to improve safety and tolerability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rituximab (anti-CD20) in neurological disorders]. Akaishi, T., Nakashima, I.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Tocilizumab for the treatment of rheumatoid arthritis. [2016]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Intravenous tocilizumab: a review of its use in adults with rheumatoid arthritis. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Tocilizumab: new drug. Rheumatoid arthritis: another 'mab', no therapeutic advantage. [2016]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Tocilizumab: a review of its use in the management of rheumatoid arthritis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: a retrospective analysis of patients treated at a US centre. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Tendonitis and Tendon Rupture After Treatment With Rituximab: A Case Series. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Rituximab-induced vasculitis: A case report and review of the medical published work. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

[Rituximab (anti-CD20) in neurological disorders]. [2015]