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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether siltuximab (also known as Sylvant) can reduce symptoms like weakness, fatigue, and nausea after a stem cell transplant for multiple myeloma or systemic amyloidosis. The goal is to determine if blocking Interleukin-6 (IL-6), a protein involved in inflammation, can improve recovery and quality of life. Participants should have multiple myeloma or AL amyloidosis, be undergoing a stem cell transplant, and experience symptoms affecting daily life. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

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.

Is there any evidence suggesting that siltuximab is likely to be safe for humans?

A previous study found that the safety of siltuximab was similar to a placebo. Most side effects were mild to moderate, though some serious ones occurred. Another study showed that siltuximab is generally well-tolerated, even with long-term use. This suggests that siltuximab might be safe for treating conditions like multiple myeloma. While some individuals may experience side effects, the overall evidence supports its use under medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Siltuximab is unique because it targets interleukin-6 (IL-6), a protein that plays a significant role in the growth of multiple myeloma cells. Unlike standard treatments like chemotherapy and proteasome inhibitors, which broadly target cancer cells, siltuximab specifically blocks IL-6, potentially reducing side effects and enhancing effectiveness. Researchers are excited about siltuximab because it offers a targeted approach, which could lead to better outcomes for patients with multiple myeloma by effectively slowing down or stopping the cancer's progression.

What evidence suggests that siltuximab might be an effective treatment for multiple myeloma?

Research has shown that siltuximab, a drug that blocks a protein called IL-6 involved in inflammation, may help with certain issues related to multiple myeloma. In this trial, participants will receive siltuximab, which has shown promise in previous studies. Specifically, studies found that people taking siltuximab experienced fewer instances of disease progression compared to those taking a placebo. For instance, in one study, 32.6% of participants had disease progression with siltuximab, while 42.9% did with a placebo. Although the results were not as high as expected, there was still a noticeable positive effect. This suggests that siltuximab might help reduce symptoms after stem cell transplants by controlling inflammation. ^{1 4 5 6 7}

Who Is on the Research Team?

Gunjan Shah, MD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30890552/

Randomized, Double-Blind, Placebo-Controlled, ... This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01266811

NCT01266811 | A Phase 3 Study of Siltuximab or Placebo ... The purpose of this study is to determine if there is an improvement in progression-free survival (length of time during and after treatment in which a ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119836716

A Phase 2, Randomized, Double-Blind, Placebo- ... After a median follow-up of 29.2 months, there were 32.6% PFS events (14/43 pts) in the siltuximab group and 42.9% (18/42 pts) in the placebo ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/25/13/3772/81594/Randomized-Double-Blind-Placebo-Controlled

Randomized, Double-Blind, Placebo-Controlled, Multicenter ... After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with ...

5. multiplemyelomahub.com multiplemyelomahub.com/medical-information/siltuximab-for-high-risk-smoldering-multiple-myeloma

Siltuximab for high-risk smoldering multiple myeloma Siltuximab led to an absolute improvement in 1-year PFS rate of 10.1% meaning the study did not meet the hypothesized improvement of 14%. With ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00402181

An Efficacy and Safety Study of Siltuximab in Participants ... The purpose of this study is to evaluate the safety and efficacy of siltuximab in participants with relapsed (the return of a disease or the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32027862/

Long-term safety of siltuximab in patients with idiopathic ... These results show that siltuximab is well tolerated long term and provides important evidence for the feasibility of the life-long use required by patients.