Rituximab or Tocilizumab for Immune-Related Side Effects

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, rituximab and tocilizumab, to manage side effects from cancer immunotherapy, especially when long-term steroid use is necessary. These side effects arise when the immune system becomes overactive. The trial seeks to determine if these treatments, which have helped with similar immune issues in other conditions, can also be effective here. Suitable participants have advanced solid tumors and have developed immune-related problems from cancer treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both tocilizumab and rituximab have been studied for safety in various conditions. Tocilizumab is generally well-tolerated. One study found no major side effects in patients using it for immune-related issues, except for one case where the disease worsened 18 months later. However, in a larger group, 77.3% of patients experienced side effects, though these were not severe.

Rituximab presents a different safety profile. Common side effects include infections, nausea, diarrhea, headaches, muscle spasms, and swelling, affecting more than 15% of patients. Some individuals also report reactions during infusions and fever.

Both treatments have approval for other conditions, indicating a well-understood safety profile. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because Rituximab and Tocilizumab offer new approaches to managing immune-related side effects (irAEs) from cancer therapies. Unlike traditional treatments that often rely on steroids to suppress the immune system, Rituximab targets B-cells, a type of white blood cell involved in the immune response, which could provide a more focused intervention. Tocilizumab works differently by blocking the IL-6 receptor, a key player in inflammation, offering potential relief for patients who might not respond well to steroids. Both treatments provide fresh strategies that could lead to more effective and tailored management of irAEs, with potentially fewer side effects than conventional options.

What evidence suggests that rituximab or tocilizumab could be effective for treating immune-related side effects?

This trial will compare the effectiveness of Tocilizumab and Rituximab in treating immune-related side effects in patients with advanced solid tumors. Research has shown that Tocilizumab effectively treats immune system-related side effects. In one study, 85% of patients benefited without their cancer worsening. Another study found that 81% of patients experienced significant improvements with Tocilizumab.

For Rituximab, studies indicate it is effective in about 67% of cases for conditions like myasthenia gravis, which also involve the immune system. These treatments work by calming parts of the immune system, reducing unwanted side effects. Participants in this trial will receive either Tocilizumab or Rituximab to assess their effectiveness in managing immune-related side effects. ^{1 2 6 7 8}

Who Is on the Research Team?

Brian Henick, MD

Principal Investigator

Assistant Professor of Medicine in the Division of Hematology and Oncology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

1.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(20)43200-4/fulltext

Effectiveness of rituximab in treating immune-checkpoint ...

Rituximab was reportedly effective in six of nine patients (67%) who presented with myasthenia gravis, Sjögren's syndrome and Sjögren's syndrome ...

2.

rituxan-hcp.com

rituxan-hcp.com/ra/efficacy/safety-data.html

RA | Safety Data & Possible Side Effects | RITUXAN® (rituximab)

Among all exposed patients, adverse reactions reported in greater than 10% of patients include infusion-related reactions, upper respiratory tract infection, ...

3.

riabni.com

riabni.com/rheumatoid-arthritis/rituximab-biosimilar-efficacy

Rituximab Biosimilar Efficacy

Deaths within 24 hours of rituximab infusion have occurred. Approximately 80% of fatal infusion-related reactions occurred in association with the first ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6806017/

Long‐Term Safety of Rituximab in Patients With ...

This study shows long‐term safety data for 989 patients with RA who were treated with rituximab. The study provides extensive characterizations of clinically ...

5.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2020/761140s000lbl.pdf

RIABNI (rituximab-arrx) injection, for intravenous use

Based on human data, rituximab products can cause adverse developmental outcomes including B-cell lymphocytopenia in infants exposed in utero (see Clinical ...

6.

rituxan-hcp.com

rituxan-hcp.com/pv/efficacy/safety.html

PV | RITUXAN® (rituximab) Safety Data

Adverse reactions reported in ≥15% of Rituxan-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, infusion- ...

7.

riabni.com

riabni.com/rheumatoid-arthritis

Rituxan® Biosimilar

Adverse reactions reported in ≥15% of rituximab-treated patients were infections, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema, infusion- ...

8.

ashpublications.org

ashpublications.org/blood/article/140/Supplement%201/13196/487365/Comparison-of-Adverse-Event-Profiles-of-Rituximab

Comparison of Adverse Event Profiles of Rituximab, Rituximab ...

Rituximab-abbs had the lowest odds of causing respiratory (ROR 3.34, 2.90-3.85), skin (ROR 4.80, 4.15-5.55) and immune-related events (ROR 1.76, ...