Ruxolitinib in Previously Treated Idiopathic Multicentric Castleman Disease

NCT07085039 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 858269
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The research study is being done to look at the effects of ruxolitinib in adults with idiopathic Multicentric Castleman Disease (iMCD) that has not gotten better from taking siltuximab or tocilizumab, or who cannot take those medications.

Conditions

Castleman's Disease (CD); Idiopathic Multicentric Castleman's Disease

Outcome Measures

Primary Outcomes (1)

• The proportion of participants achieving a positive Clinical Benefit Response (CBR) response at 12 months ± 1 month. Assessments at 12 months ± 1 month. will be compared to those at the baseline visit

  Clinical Benefit Response (CBR):CBR is defined by improvements in clinical symptoms (fatigue, anorexia, fever and night sweats). Laboratory markers like Hemoglobin levels, weight change and lymph node size are included in the CBR. A CBR is considered positive if there is at least a 25% reduction in the size of the largest lymph node (measured by modified Cheson criteria), a significant improvement in at least one laboratory marker (e.g., hemoglobin), and improvement in at least one clinical symptom without worsening of others. Positive response: Relative to baseline, improvement in at least one of the criterion without worsening of any single criterion other than hemoglobin on two consecutive study visits. Negative response: Relative to baseline, worsening of any single criterion other than hemoglobin on two consecutive site visits or failure to achieve improvement for any criterion.

  12 months ± 1 month

Secondary Outcomes (6)

• The proportion of participants achieving a positive CBR response at 3, 6, 9 months compared to baseline

  3, 6, and 9 months compared to baseline

• Disease activity, as measured by the CHAP scale, at 3, 6, 9, and 12 months ± 1 month. Assessments will be compared to those obtained at the Baseline Visit

  3, 6, 9, and 12 months ± 1 month

• Disease activity, as measured by MCD-related Overall Symptom Score as measured by 34 outcome measures at 3, 6, 9, and 12 months ± 1 month compared to those obtained at the Baseline Visit

  3, 6, 9, and 12 months ± 1 month

• The proportion of participants achieving a lymph node response, following the modified Cheson response criteria compared to baseline

  Month 12

• The proportion of participants that remain on study drug for the duration of the study

  Up to 73 weeks

Other Outcomes (1)

• All serious adverse events (SAEs) or Grade 3 or higher adverse events (AEs) related to ruxolitinib will be assessed.

  12 months

Study Arms (1)

Ruxolitinib

OTHER

This is an open-label study so all patients will be assigned to the same interventional arm and given ruxolitinib

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

Participants will take the study drug in a tablet form, by mouth, every day for the next year, as long as it is helping with their disease and not causing unacceptable side effects.

Ruxolitinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18-80
• Documented disease history consistent with diagnostic criteria for iMCD
• Indication of clinico-histopathological features consistent with iMCD as determined by a licensed pathologist in a diagnostic pathology report, or a CAS grade of at least 3 in the companion registry study (ACCELERATE).
• Refractory (patient did not achieve sufficient disease control with anti-IL-6 therapy, as determined by the site investigator), relapsed (return of symptoms while on therapy), or inability to tolerate anti-IL-6 or anti-IL-6 receptor therapy
• Evidence of active disease, defined by at least two of: constitutional symptoms (fatigue, night sweats, fever, weight change), hemoglobin \< lower limit of normal, C-reactive protein \> upper limit of normal (or \>10 mg/L), or albumin \< lower limit of normal (\<3.5 g/dL), at lease one lymph node meeting modified Cheson criteria
• Ability to consume oral medication in the form of a tablet
• Ability to provide informed consent prior to any study-specific activities

You may not qualify if:

• Subjects cannot be pregnant or nursing females
• Women of childbearing potential must have a negative pregnancy test documented at the Baseline Visit. Subjects of reproductive potential may not participate unless they have agreed, as part of the informed consent, to use an effective contraceptive method for the duration of the study and for at least 12 weeks after ending treatment
• Subjects cannot have received any systemic therapy(ies) intended to treat iMCD other than corticosteroids or anti-IL-6 therapy within 14 days of enrollment
• Corticosteroid treatment must have been initiated more than 28 days prior to enrollment and be maintained at a stable or tapering dose (prednisone or equivalent up to 1 mg/kg/day) prior to enrollment; dose cannot be elevated for the duration of the study but can be maintained or tapered
• For subjects who cannot or are unwilling to undergo a 14-day washout period from their anti-IL-6 therapy: i. Anti-IL-6 therapy may be permitted if the subject has been on therapy for at least 3 months, no toxicity has been documented, and sufficient disease control is not achieved ii. Anti-IL-6 therapy is recommended to be discontinued within the first 6 weeks after starting ruxolitinib
• Subjects cannot have previously received ruxolitinib monotherapy or combination therapy to treat iMCD
• Fungal disease must be stable for at least two weeks before enrollment
• Subjects with history of recent bacteremia must have a documented negative blood culture before enrollment
• Subjects with past history of non-therapy related opportunistic infection should discuss eligibility and possible immunologic evaluation with the licensed site investigator prior to enrollment
• Subjects cannot have:
• ECOG \>3
• eGFR \<30mL/min/1.73 m2 or creatinine \>3.0 mg/dL
• Absolute neutrophil count (ANC) \< 1000 x 109/L
• Hemoglobin ≤ 6.5 g/dL (transfusion independent, defined as not receiving a red blood cell transfusion for ≥ 7 days prior)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory values greater than three times the upper limit of normal

Sponsors & Collaborators

• University of Pennsylvania: lead
• Incyte Corporation: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Castleman Disease

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Joshua Brandstadter, MD, PhD, MSc

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bridget Austin, MS

CONTACT

267-586-9977; bridget.austin@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: July 25, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 22, 2026

Record last verified: 2026-04

Locations

US (1)