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Multiple MyelomaPhase 2NCT06352866

Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to tx w/ Teclistamab in RRMM

A Phase 2 study testing Siltuximab and Teclistamab(FDA-approved) in people with Multiple Myeloma and Cytokine Release Syndrome, run by Jack Khouri, MD at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to examine the safety, efficacy and feasibility of the use of one standard dose of siltuximab prior to teclistamab infusion. Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Siltuximab and Teclistamab(FDA-approved)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
1 Jan 2025to 1 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults 18 years of age and older.
  • Relapsed or refractory measurable multiple myeloma following prior treatment with ≥4 lines of anti-myeloma therapy slated for teclistamab monotherapy
  • Adequate bone marrow function including:
  • Hemoglobin ≥ 8g/dL (unless ≥50% bone marrow involvement by MM),
  • Absolute neutrophil count >1000 / µL (unless bone marrow involvement by MM)
  • Platelet count ≥30,000 / µL (unless bone marrow involvement by MM)
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  • ECOG performance status 0 - 2
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 3 months after the last dose of siltuximab.
  • A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (< 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
  • Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period. Men must refrain from donating sperm during this same period.
  • With pregnant female partners, men must remain abstinent or use a condom during the treatment period.
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.

Who cannot join

  • Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or AL amyloidosis.
  • Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome.
  • Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status (Attachment 10). Hepatitis C (anti-hepatitis C virus [HCV] antibody positive or HCV-RNA quantitation positive) or known to have a history of hepatitis C. If positive, further testing of quantitative levels to rule out positivity is required.
  • Active central nervous system or meningeal involvement by MM.
  • Active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic therapy within 2 weeks prior to first dose of study drug.
  • Active malignancy except for any of the following:
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  • Adequately treated cutaneous basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
  • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for 2 years
  • Low-risk prostate cancer with Gleason score <7, prostate-specific antigen <10 ng/mL, and a stage of cancer at most cT2a, cN0, and CM0
  • Any other cancer from which the subject has been disease-free for ≥2 years
  • Participants with uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women are excluded from this study because siltuximab therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with siltuximab, breastfeeding should be discontinued during treatment and for 3 months after the last dose of siltuximab. These potential risks may also apply to other agents used in this study.
  • Participants with history of clinically relevant and active CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
  • Participants with history of severe hypersensitivity reaction to siltuximab or any of the excipients

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: Phase II Trial of Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to Treatment With Teclistamab in Relapsed or Refractory Multiple Myeloma (RRMM)

The purpose of this study is to examine the safety, efficacy and feasibility of the use of one standard dose of siltuximab prior to teclistamab infusion. Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). IL-6 is a cytokine; these are products that are secreted by certain cells of the immune system and effect other cells in participant's body. IL-6 regulates immune, inflammatory and metabolic processes. Siltuximab has already been tested and approved for use by the FDA in participants with a condition called multicentric Castleman's disease, which is a lymphoproliferative disorder. This study is being conducted to investigate if administration of a single dose of siltuximab will reduce the rates of and severity of Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) in participants prior to teclistamab administration. CRS and ICANS are adverse effects commonly experienced by participants being treated with teclistamab that are related to inflammation in the body. Siltuximab is experimental because it is not approved by the Food and Drug Administration (FDA) for prophylactic use prior to administration of teclistamab infusion.

Read the detailed description

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are clinically relevant toxicities of bsAbs and other T cell redirecting therapies. The armamentarium of immunotherapeutic approaches is expected to grow at exponential rates in the upcoming years, with an expansion of the diseases treated with this modality.

While the risk of CRS and ICANS is limited with most bsAbs(bispecific antibodies), these side effects can prevent a more widespread adoption of these therapies and impede their use in participants for whom access to tertiary or quaternary medical centers is limited.

The development of strategies that prevent CRS and ICANS occurring after bispecific antibodies can increase the prescription of these effective immunotherapies, in particular for participants for whom access to care is limited.

Siltuximab is a chimeric murine antibody that binds directly to IL-6 and has been used effectively in the treatment of CRS, with guidelines recommending its use in CRS cases refractory to tocilizumab.

Study hypothesis is that, through direct binding of IL-6, siltuximab can overcome the risk of increased IL-6 - mediated ICANS by decreasing the available IL-6 for blood brain barrier passage and by facilitating clearance of IL-6 through IL-6 receptor-mediated mechanisms.

Based on this rationale, a phase II study investigating the use of siltuximab for CRS and ICANS prophylaxis prior to therapy with the BCMAxCD3 bispecific antibody teclistamab.

This study will examine the safety, efficacy and feasibility of the use of standard doses of siltuximab prior to teclistamab infusion and will determine the rates of all grades as well as grade 2 or higher CRS and ICANS in participants given prophylaxis prior to teclistamab, which has well defined rates of CRS and ICANS. This will allow for a preliminary assessment of the efficacy of siltuximab as preventive measure against CRS and ICANS.

Being tested
Siltuximab, Teclistamab(FDA-approved)
Keywords
Multiple Myeloma
Medical subject headings
Multiple Myeloma, Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SiltuximabDrug

    Siltuximab is an investigational (experimental) drug that works by binding directly to human interleukin-6 (IL-6). IL-6 is a cytokine; these are products that are secreted by certain cells of the immune system and effect other cells in participant's body. IL-6 regulates immune, inflammatory and metabolic processes. Siltuximab has already been tested and approved for use by the FDA in participants with a condition called multicentric Castleman's disease, which is a disorder of the lymphatic system

  • Teclistamab(FDA-approved)Drug

    Teclistamab is a FDA-approved drug for the treatment of advanced MM after 4 lines of therapy.

Study groups in NCT06352866
Study groupRoleWhat they receive
SiltuximabExperimentalParticipants will receive a single dose of prophylactic siltuximab, 11 mg/kg, 2 hours prior to the administration of the first dose of teclistamab on day 1. There is no planned dose escalation of siltuximab, and teclistamab dosing will be done following the standard planned ramp-up mentioned below. Participants will be hospitalized for 9 days according to teclistamab package insert and Cleveland Clinic institutional practice. Participants will be followed for the incidence of CRS and ICANS for the first two 22-day cycles of treatment.
Receives: Drug: Siltuximab; Drug: Teclistamab(FDA-approved)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in CRS Rate

    ASTCT criteria will be used to report CRS

    Measured: First two 22-day cycles after treatment initiation or until death, whichever occurs first.

Secondary outcomes (8)
  1. Safety assessment of a single dose of siltuximab as CRS prophylaxis

    Adverse events graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: From the start of the infusion of the first dose of siltuximab until 22 days.

  2. Incidence of grade ≥ 2 cytokine release syndrome after siltuximab prophylaxis

    Response to siltuximab prophylaxis will be measured by incidence of all grade CRS and grade ≥ 2 CRS. Grading will be done according to the ASTCT consensus criteria

    Measured: First two 22-day cycles after treatment initiation or until death, whichever occurs first.

  3. Incidence of all grade ICANS after siltuximab prophylaxis

    Grading will be done according to the ASTCT consensus criteria

    Measured: First two 22-day cycles after treatment initiation or until death, whichever occurs first.

  4. Incidence of adverse events after siltuximab prophylaxis

    Adverse events will be graded according to NCI CTCAE Version 5.0

    Measured: First two 22-day cycles after treatment initiation or until death, whichever occurs first

  5. Overall response rate

    Survival rates will be calculated using Kaplan Meier method

    Measured: 6 months after treatment initiation or until disease progression, whichever comes first.

  6. Progression free survival

    Survival rates will be calculated using Kaplan Meier method

    Measured: 6 months after treatment initiation or until disease progression, whichever comes first.

  7. Overall survival

    Survival rates will be calculated using Kaplan Meier method

    Measured: 6 months after treatment initiation or until disease progression, whichever comes first.

  8. Hospitalization rates

    Percentage as measured by Karnofsky Performance Scale to monitor hospitalization rates from 0 to 100, where 0 being death and 100 being normal, no complaints, no evidence of disease

    Measured: First two 22-day cycles after treatment initiation or until death, whichever occurs first

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2024
  2. Study start1 Jan 2025 (estimated)
  3. Primary completion1 Apr 2025 (estimated)
  4. Study completion1 Dec 2025 (estimated)

Why it stopped: Funding unavailable

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
Model description
This study is an open label single cohort feasibility and efficacy study of siltuximab prophylaxis prior to infusion of teclistamab for treatment of RRMM. There is no planned dose escalation and no separate cohorts. Participants will receive a single dose of prophylactic siltuximab, 11 mg/kg, 2 hours prior to the administration of the first dose of teclistamab on day 1. There is no planned dose escalation of siltuximab, and teclistamab dosing will be done following the standard planned ramp-up. Participants will be hospitalized for 9 days according to teclistamab package insert and Cleveland Clinic institutional practice. Participants will be followed for the incidence of CRS and ICANS for the first two 22-day cycles of treatment.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06352866
Sponsor's protocol ID
CASE3A23
Status last verified
Feb 2025
First submitted
2 Apr 2024
Last updated
3 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Publications are expected to result from this trial. Individual participant data will not be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Siltuximab and Teclistamab(FDA-approved) in people with Multiple Myeloma and Cytokine Release Syndrome, run by Jack Khouri, MD at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in CRS Rate (time frame: First two 22-day cycles after treatment initiation or until death, whichever occurs first.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025.

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