Siltuximab for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: IL-6 inhibitors

Disqualifiers: Other malignancy, Autoimmune disease, HIV, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing siltuximab, a medication that blocks a protein called IL-6, to help reduce severe symptoms like weakness and fatigue after a stem cell transplant. The target group is patients aged 60-75 with multiple myeloma or systemic amyloidosis. By reducing inflammation, the goal is to improve recovery and shorten hospital stays.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Siltuximab for treating multiple myeloma?

Research shows that Siltuximab, when combined with other drugs like lenalidomide, bortezomib, and dexamethasone, resulted in a high response rate in newly diagnosed multiple myeloma patients, with 90.9% showing some level of positive response. Additionally, Siltuximab has been shown to enhance the effectiveness of melphalan, another drug used in treating multiple myeloma, by increasing cancer cell death in laboratory studies. ^{1 2 3 4 5}

Is siltuximab generally safe for humans?

Siltuximab has been tested in various studies and is generally well tolerated in humans. Common side effects include skin itching, weight gain, rash, and upper respiratory infections, while serious side effects like pneumonia and low platelet counts have been observed in some cases. No deaths were reported in the studies reviewed. ^{1 4 6 7 8}

How is the drug siltuximab unique in treating multiple myeloma?

Siltuximab is unique because it targets interleukin-6 (IL-6), a protein that plays a key role in the development of multiple myeloma, by using a monoclonal antibody to inhibit its activity. This approach is different from other treatments that may not specifically target IL-6, and it is administered intravenously every two weeks. ^{1 2 3 4 6}

Research Team

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for individuals aged 60-75 with multiple myeloma or AL amyloidosis, undergoing stem cell transplant. They must have good lung function and enough CD34+ cells for infusion, stable clinical lab values, and agree to use contraception if necessary. Exclusions include recent major surgery or infection, prior IL-6 targeting treatment, other active malignancies within 2 years (with exceptions), significant concurrent illnesses, live vaccinations within 4 weeks before the study starts, certain infections like HIV/Hepatitis B/C, recent investigational drug/device use.

Inclusion Criteria

Your recent medical test results need to meet certain standards set by the study.

I am a man who will use protection during sex with a woman who can have children.

I can care for myself and perform daily activities.

Exclusion Criteria

A woman who is pregnant or breast-feeding, or a woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study agent

Concurrent medical condition or disease likely to interfere with study procedures or results, or constitute a hazard for participating in the study

I do not have HIV, hepatitis C, or active hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Treatment

Siltuximab 11mg/kg is administered seven days before autologous stem cell infusion

1 week

1 visit (in-person)

Post-Transplant Treatment

Siltuximab 11mg/kg is administered 21 days after autologous stem cell infusion

3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Siltuximab
• The M.D. Anderson Symptom Inventory (MDASI)

Trial Overview The trial tests whether Siltuximab can reduce symptoms such as weakness and nausea after autologous stem cell transplantation by blocking a protein called Interleukin-6 (IL-6). Participants will receive Siltuximab before and after their transplant to see if it improves recovery and quality of life during the post-transplant period.

Participant Groups

Group I: Siltuximab Experimental Treatment 2 Interventions

Siltuximab 11mg/kg will be administered seven days before and 21 days after autologous stem cell infusion (+/-2 day).

Siltuximab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Sylvant for:

• Multicentric Castleman's disease

Approved in United States as Sylvant for:

• Multicentric Castleman's disease

Approved in Canada as Sylvant for:

• Multicentric Castleman's disease

Approved in Japan as Sylvant for:

• Multicentric Castleman's disease

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

In a study of 14 patients with newly diagnosed multiple myeloma, the combination of siltuximab with lenalidomide, bortezomib, and dexamethasone showed a high overall response rate of 90.9%, indicating strong efficacy in treating this condition.

The maximum tolerated dose of siltuximab was determined to be 8.3 mg/kg, with serious adverse events including grade 3 pneumonia and grade 4 thrombocytopenia, but no deaths occurred during the study, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial. Shah, JJ., Feng, L., Thomas, SK., et al.[2018]

The IL-6-neutralizing monoclonal antibody siltuximab enhances the effectiveness of melphalan, a chemotherapy drug, against multiple myeloma cells, showing additive to synergistic effects in various human myeloma cell lines.

Siltuximab not only increases the cytotoxicity of melphalan but also promotes apoptosis through the activation of key caspases and suppression of the IL-6 signaling pathway, suggesting a promising combination therapy for patients with myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. Hunsucker, SA., Magarotto, V., Kuhn, DJ., et al.[2021]

Siltuximab was approved by the FDA for treating multicentric Castleman disease (MCD) in HIV-negative and HHV-8-negative patients, based on a randomized trial with 79 patients showing a significant response rate; 34% of those treated with siltuximab achieved a durable tumor and symptomatic response compared to none in the placebo group.

The treatment was generally well-tolerated, with common side effects including pruritus, increased weight, rash, hyperuricemia, and upper respiratory tract infections occurring in more than 10% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Deisseroth, A., Ko, CW., Nie, L., et al.[2017]

References

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

Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial. [2018]

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

A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. [2021]

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

A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Evaluation of the QTc prolongation potential of a monoclonal antibody, siltuximab, in patients with monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or low-volume multiple myeloma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. [2021]

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

FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. [2017]

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

A phase 1, randomized study to assess the pharmacokinetic comparability of siltuximab derived from two different cell lines in healthy subjects. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Phase 1 study in Japan of siltuximab, an anti-IL-6 monoclonal antibody, in relapsed/refractory multiple myeloma. [2018]