Siltuximab In Siltuximab-RElapsed/REfractory Multicentric CAstleman Disease

NCT04838860 | Terminated Phase 2 FDA Drug

• 1 other identifier: EUSA SYL 0002
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 2 study to investigate the safety, tolerability, and efficacy of administering increased siltuximab doses to patients with iMCD

Conditions

Idiopathic Multicentric Castleman's Disease

Outcome Measures

Primary Outcomes (1)

• 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).

  12 Weeks

Secondary Outcomes (11)

• To evaluate the safety and tolerability of increased Siltuximab doses

  12 Weeks

• Pharmacokinetics (Vd)

  12 Weeks

• Pharmacokinetics (CL)

  12 Weeks

• Pharmacokinetics (AUC)

  12 Weeks

• Pharmacokinetics (Cmin / Cmax)

  12 Weeks

Study Arms (2)

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.

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.

Drug: Siltuximab

Interventions

Siltuximab DRUG

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.

Also known as: Sylvant

Parallel Arm of TAFRO-iMCD Patients; Parallel Arm of iMCD Patients

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• RECORDATI GROUP: lead

Study Sites (1)

Edward W. Sparrow Hospital

Lansing, Michigan, 48912, United States

Location

MeSH Terms

Conditions

Multi-centric Castleman's Disease

Interventions

siltuximab

Study Officials

• Chris Keuker, MD

  Syneos Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Record Dates

• First Submitted: February 25, 2021
• First Posted: April 9, 2021
• Study Start: March 31, 2021
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: April 19, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)