Trial Title:
Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to tx w/ Teclistamab in RRMM
NCT ID:
NCT06352866
Condition:
Multiple Myeloma
Cytokine Release Syndrome
Refractory Multiple Myeloma
Immune Effector Cell Associated Neurotoxicity Syndrome
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neurotoxicity Syndromes
Syndrome
Cytokine Release Syndrome
Siltuximab
Conditions: Keywords:
Multiple Myeloma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention 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.
Primary purpose:
Supportive Care
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Siltuximab
Description:
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
Arm group label:
Siltuximab
Intervention type:
Drug
Intervention name:
Teclistamab(FDA-approved)
Description:
Teclistamab is a FDA-approved drug for the treatment of advanced MM after 4 lines of
therapy.
Arm group label:
Siltuximab
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). 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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adults 18 years of age and older.
2. Relapsed or refractory measurable multiple myeloma following prior treatment with ≥4
lines of anti-myeloma therapy slated for teclistamab monotherapy
3. 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)
4. ECOG performance status 0 - 2
5. 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.
6. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, and agreement to refrain from donating sperm, as defined
below:
1. 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.
2. 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.
Exclusion Criteria:
1. Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or AL amyloidosis.
2. Known to be seropositive for human immunodeficiency virus or acquired immune
deficiency syndrome.
3. 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.
4. Active central nervous system or meningeal involvement by MM.
5. Active bacterial, viral, fungal, mycobacterial, parasitic or other infection
requiring systemic therapy within 2 weeks prior to first dose of study drug.
6. Active malignancy except for any of the following:
- 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
7. 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.
8. 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.
9. 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.
10. Participants with history of severe hypersensitivity reaction to siltuximab or any
of the excipients
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Contact:
Last name:
Jack Khouri, MD
Phone:
866-223-8100
Email:
TaussigResearch@ccf.org
Investigator:
Last name:
Jack Khouri, MD
Email:
Principal Investigator
Start date:
January 1, 2025
Completion date:
December 1, 2025
Lead sponsor:
Agency:
Jack Khouri
Agency class:
Other
Source:
Case Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06352866
