Idiopathic Multicentric Castleman's DiseasePhase 2SISREMCADNCT04838860
Siltuximab In Siltuximab-RElapsed/REfractory Multicentric CAstleman Disease
A Phase 2 study testing Siltuximab in people with Idiopathic Multicentric Castleman's Disease, run by RECORDATI GROUP at 1 site in United States.
Trial summary
Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Idiopathic Multicentric Castleman's Disease
- What is being tested?
- Siltuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2021to 1 Apr 2021
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented history of consensus histologic, laboratory, and clinical diagnostic criteria of iMCD.
- Archival and/or baseline incisional/excisional biopsy for retrospective central histologic confirmation of iMCD.
- CDCNRC-defined disease progression on or after prior treatment with siltuximab at 11 mg/kg q3w without unacceptable toxicity within 12 weeks between the last dose of siltuximab and the date of signed patient informed consent form (ICF).
- At least 1 measurable abnormal lymph node mass that is ≥1 cm in its longest transverse diameter as assessed by computerized tomography (CT) scan that has not been previously irradiated.
- Elevated (>10 mg/L) and rising serum CRP in the absence of additional iMCD treatment.
- Evidence of at least an additional one of the following laboratory or clinical signs of iMCD per international, evidence-based consensus diagnostic criteria for HIV or HHV 8-negative iMCD:
Show all 13Show fewer
- Anemia, thrombocytopenia, hypoalbuminemia, renal dysfunction, or polyclonal hypergammaglobulinemia.
- Constitutional symptoms (night sweats, fever (>38°C), weight loss, or fatigue (CTCAE lymphoma B-symptoms score ≥2), large spleen and/or liver, fluid accumulation, eruptive cherry hemangiomatosis/violaceous papules, or lymphocytic interstitial pneumonitis.
- Adequate clinical laboratory measurements within 3 weeks prior to study entry in all parameters below:
- Absolute neutrophil count ≥1.0 × 109/L, hemoglobin <17 g/dL, and platelets ≥50 × 109/L without transfusion, hematopoietic growth factors, or both for >7 days prior to measurement.
- AST, ALT, total bilirubin, and alkaline phosphatase ≤5 × ULN.
- Fasting cholesterol <300 mg/dL and fasting triglyceride <400 mg/dL.
- Age ≥12 years.
Who cannot join
- Documentation of HIV or HHV-8 infection or presence of other infection-related disorders that resemble clinical or histological features of iMCD
- Diagnosis of any malignant/benign lymphoproliferative disorders
- Diagnosis of autoimmune/autoinflammatory disease
- Treatment with corticosteroids (prednisone dose-equivalent >1 mg/kg/day) within 7 days prior to study entry.
- History of solid organ transplant, allogeneic bone marrow transplant, or allogeneic peripheral blood stem cell transplant.
- Previous malignancy with the following exceptions:
- Past malignancy with treatment that was completed at least 2 years before signing informed consent and the patient has no evidence of disease, or
- Concurrent malignancy that is clinically stable and does not require tumor-directed treatment (eg, nonmelanoma skin cancer and carcinoma in situ)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Study of Intrapatient Siltuximab Dose Escalation in Patients With Idiopathic Multicentric Castleman Disease That Has Progressed After Prior Siltuximab Treatment
Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD
Read the detailed description
This is an open-label, two-stage, Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD who progressed with elevated and rising serum C reactive protein (CRP) levels after prior treatment with siltuximab 11 mg/kg every 3 weeks (q3w) without unacceptable toxicity, and is primarily designed to leverage opportunities for intrapatient dose escalation with available clinical, nonclinical, and PK justification as a means to restore or enable disease control.
Enrolling in Stage 1a and Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD and TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below.
- Being tested
- Siltuximab
- Medical subject headings
- Multi-centric Castleman's Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiltuximabDrug
Also called Sylvant
Participants will receive intravenous (IV) infusion of siltuximab 22 mg/kg over 2 hours every 3 weeks, then possibly dose escalating to 33 mg/kg IV over 3 hours +/- 44 mg/kg IV over 4 hours every 3 weeks if clinically indicated in the absence of dose-limiting toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Parallel Arm of iMCD Patients | Active comparator | Enrolling in Stage 1a of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below. Receives: Drug: Siltuximab |
| Parallel Arm of TAFRO-iMCD Patients | Active comparator | Enrolling in Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below. Receives: Drug: Siltuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the Clinical Benefit Response (CBR) of Siltuximab
Assess the clinical benefit response (CBR) of increased siltuximab doses in patients with IL-6-driven (C-reactive protein [CRP]-elevated and rising) idiopathic multicentric Castleman disease (iMCD) after disease progression on the standard siltuximab dose schedule. CBR defined as complete response (CR), partial response (PR), or stable disease (SD) lasting ≥12 weeks per Castleman Disease Collaborative Network Response Criteria (CDCNRC).
Measured: 12 Weeks
Secondary outcomes (11)
To evaluate the safety and tolerability of increased Siltuximab doses
Incidence of Adverse Events (AEs), serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), incidence of abnormal laboratory test results incidence of dose-limiting toxicities (DLTs)
Measured: 12 Weeks
Pharmacokinetics (Vd)
To test the patient's drug propensity
Measured: 12 Weeks
Pharmacokinetics (CL)
To test the volume of plasma cleared of drug per unit time
Measured: 12 Weeks
Pharmacokinetics (AUC)
To test the extent of exposure to a drug and its clearance rate from the body
Measured: 12 Weeks
Pharmacokinetics (Cmin / Cmax)
To test the minimum (Cmin) and the maximum (Cmax) blood plasma concentration
Measured: 12 Weeks
Pharmacokinetics (Ctrough)
To test the minimum drug concentration after a dose
Measured: 12 Weeks
Pharmacokinetics (Tmax)
To test the time taken to reach Cmax
Measured: 12 Weeks
Evaluate the efficacy of increased siltuximab doses after disease progression on prior siltuximab treatment.
The primary efficacy endpoint is CBR defined as CR, PR, or SD lasting ≥12 weeks per CDCNRC based on evaluation of biochemical, lymph node, and symptom response
Measured: 12 Weeks
Evaluate the immunogenicity of increased siltuximab doses after disease progression on prior siltuximab treatment.
Immunogenicity will be assessed through the detection of antibodies against siltuximab, and will be conducted via immunoassay ± serum IL-6 levels on Day 1 of Cycle 1, 3, 6 and every 4 cycles thereafter, before administration of siltuximab.
Measured: 12 Weeks
To evaluate the patient-reported outcomes (PROs) using the EQ-5D Instrument
The secondary outcome measures will include the health status measures of the EuroQuality of Life Five Dimensions (EQ-5D) has the following dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the 5 dimensions
Measured: 12 Weeks
To evaluate the patient-reported outcomes (PROs) using the MCD-SS Instrument
The Multicentric Castleman disease symptom score (MCD-SS) lists 10 symptoms which are graded on a scale: Did not experience (0); Very mild (2); Mild (4); Moderate (6); Severe (8); Very Severe (10). The mean score of the ten items is calculated and a higher score indicates more severe symptoms.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2021
- Study start31 Mar 2021
- Primary completion1 Apr 2021
- Study completion1 Apr 2021
Why it stopped: Internal Company Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Multicentric Castleman's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Enrolling in Stage 1a and Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD and TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below.
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- RECORDATI GROUP
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chris Keuker, MD, Study director, Syneos Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04838860
- Sponsor's protocol ID
- EUSA SYL 0002
- Acronym
- SISREMCAD
- Status last verified
- Mar 2021
- First submitted
- 25 Feb 2021
- Last updated
- 19 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Intrapatient Siltuximab Dose Escalation in Patients With Idiopathic Multicentric Castleman Disease That Has Progressed After Prior Siltuximab Treatment
- ClinicalTrials.gov ID
- NCT04838860
- Acronym / sponsor ID
- SISREMCAD / EUSA SYL 0002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Internal Company Decision
- Enrolment
- 22 participants (actual)
- Lead sponsor
- RECORDATI GROUPIndustry (pharma, biotech, devices)
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 9 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD
Detailed description
This is an open-label, two-stage, Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD who progressed with elevated and rising serum C reactive protein (CRP) levels after prior treatment with siltuximab 11 mg/kg every 3 weeks (q3w) without unacceptable toxicity, and is primarily designed to leverage opportunities for intrapatient dose escalation with available clinical, nonclinical, and PK justification as a means to restore or enable disease control.
Enrolling in Stage 1a and Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD and TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Enrolling in Stage 1a and Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD and TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below.
| Arm | Type | Receives |
|---|---|---|
| Parallel Arm of iMCD Patients | Active comparator | Drug: SiltuximabEnrolling in Stage 1a of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below. |
| Parallel Arm of TAFRO-iMCD Patients | Active comparator | Drug: SiltuximabEnrolling in Stage 1b of this study in parallel will be up to 6 patients each with siltuximab-relapsed or refractory IL-6-driven TAFRO-iMCD patients, respectively, who will undergo intrapatient dose escalation of siltuximab beginning with 22 mg/kg q3w, then possibly dose escalating to 33 mg/kg q3w then 44 mg/kg q3w if clinically indicated in the absence of DLT. The justifications for escalating siltuximab doses up to 44 mg/kg q3w will be based on intrapatient dose escalation and DLT assessments as described below. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Documented history of consensus histologic, laboratory, and clinical diagnostic criteria of iMCD.
- Archival and/or baseline incisional/excisional biopsy for retrospective central histologic confirmation of iMCD.
- CDCNRC-defined disease progression on or after prior treatment with siltuximab at 11 mg/kg q3w without unacceptable toxicity within 12 weeks between the last dose of siltuximab and the date of signed patient informed consent form (ICF).
- At least 1 measurable abnormal lymph node mass that is ≥1 cm in its longest transverse diameter as assessed by computerized tomography (CT) scan that has not been previously irradiated.
- Elevated (>10 mg/L) and rising serum CRP in the absence of additional iMCD treatment.
Key exclusion criteria (8 listed)
- Documentation of HIV or HHV-8 infection or presence of other infection-related disorders that resemble clinical or histological features of iMCD
- Diagnosis of any malignant/benign lymphoproliferative disorders
- Diagnosis of autoimmune/autoinflammatory disease
- Treatment with corticosteroids (prednisone dose-equivalent >1 mg/kg/day) within 7 days prior to study entry.
- History of solid organ transplant, allogeneic bone marrow transplant, or allogeneic peripheral blood stem cell transplant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SiltuximabAlso: SylvantParticipants will receive intravenous (IV) infusion of siltuximab 22 mg/kg over 2 hours every 3 weeks, then possibly dose escalating to 33 mg/kg IV over 3 hours +/- 44 mg/kg IV over 4 hours every 3 weeks if clinically indicated in the absence of dose-limiting toxicity. | Drug | Parallel Arm of TAFRO-iMCD Patients, Parallel Arm of iMCD Patients |
Primary outcome
Assess the Clinical Benefit Response (CBR) of Siltuximab
Time frame: 12 Weeks
Assess the clinical benefit response (CBR) of increased siltuximab doses in patients with IL-6-driven (C-reactive protein [CRP]-elevated and rising) idiopathic multicentric Castleman disease (iMCD) after disease progression on the standard siltuximab dose schedule. CBR defined as complete response (CR), partial response (PR), or stable disease (SD) lasting ≥12 weeks per Castleman Disease Collaborative Network Response Criteria (CDCNRC).
11 secondary outcomes
To evaluate the safety and tolerability of increased Siltuximab doses
Time frame: 12 Weeks
Pharmacokinetics (Vd)
Time frame: 12 Weeks
Pharmacokinetics (CL)
Time frame: 12 Weeks
Pharmacokinetics (AUC)
Time frame: 12 Weeks
Pharmacokinetics (Cmin / Cmax)
Time frame: 12 Weeks
Pharmacokinetics (Ctrough)
Time frame: 12 Weeks
Pharmacokinetics (Tmax)
Time frame: 12 Weeks
Evaluate the efficacy of increased siltuximab doses after disease progression on prior siltuximab treatment.
Time frame: 12 Weeks
Evaluate the immunogenicity of increased siltuximab doses after disease progression on prior siltuximab treatment.
Time frame: 12 Weeks
To evaluate the patient-reported outcomes (PROs) using the EQ-5D Instrument
Time frame: 12 Weeks
To evaluate the patient-reported outcomes (PROs) using the MCD-SS Instrument
Time frame: 12 Weeks
Results and safety
The study was stopped early (reason given: Internal Company Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Keuker, MD study director
Syneos Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Siltuximab in people with Idiopathic Multicentric Castleman's Disease, run by RECORDATI GROUP 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 13 inclusion and 8 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: stopped early, as of the sponsor's last update on 19 Apr 2021. 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 stopped early (reason given: Internal Company Decision). Results are not available in the source record.
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?
Assess the Clinical Benefit Response (CBR) of Siltuximab (time frame: 12 Weeks). 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 19 Apr 2021.