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Not yet recruitingNCT06643091NUCastleUpdated Oct 15, 2024

Nintedanib Treatment in Unicentric Castleman Disease

A Phase 2 interventional study of Nintedanib in Castleman Disease, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-15.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
13
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

Unicentric Castleman Disease (UCD) is a rare non-malignant localised disease involving one or more lymph nodes, associating germinal centre atrophy, mantle zone thickening and intense vascular proliferation penetrating the germinal centres. Patients usually seek medical attention because of a localised, sometimes compressive, lymph node or the development of life-threatening autoimmune complications (paraneoplastic pemphigus or PNP or myasthenia gravis or MG). The best treatment option is complete surgical excision, but it has been recently demonstrated that up to half of the patients cannot undergo surgery. In these patients, an efficient medical approach needs be defined, as no current medical treatment has demonstrated to lower morbidity and mortality. The cause of UCD is currently unknown and current data favour a scenario of stromal impairment leading to the loss of lymph node architecture rather than one of a primary hematopoietic disease. UCD lesions are often associated with synchronous follicular dendritic cell (FDC) proliferation and can sometimes evolve towards a true FDC sarcoma (FDCS), indicating a possible role for FDC, a germinal centre stromal cell component, in UCD pathogenesis. A recurrent somatic activating mutation in PDGFRB (p.N666S) has been recently described in the CD45 negative (non-hematopoietic) compartment of up to 17% UCD specimens. Moreover, activation of the VEGFR pathway is thought to play a role in the development of the disease, especially in the increased vascularity characteristic of the UCD lesion.

Nintedanib is a commercially available tyrosine-kinase inhibitor targeting PDGF, VEGF and FGF receptors. The drug has obtained European Market Authorization in 2015 for the treatment of Non-Small Cell Lung Cancer and Idiopathic Pulmonary Fibrosis with a satisfactory safety profile. The hypothesis is that nintedanib could benefit patients with unresectable or partially resectable UCD.

02

Conditions studied

  • Castleman Disease

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Keywords

  • Castleman disease
03

In context

Castleman Disease

33 studies on the registry are indexed under Castleman Disease; 10 are open to participants now.

This study's planned enrollment of 13 is below the median of 25 across 19 interventional studies indexed under Castleman Disease.

Browse Castleman Disease studies →

Lead sponsor

Assistance Publique - Hôpitaux de Paris is the lead sponsor of 3,505 studies on the registry; 1,006 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age ≥ (equal to or greater than) 18 years
  2. Written informed consent
  3. Biopsy-proven diagnosis of hyaline-vascular Unicentric Castleman disease
  4. Unresectable or partially resectable UCD lesion or surgery refusal
  5. Available oral route
  6. Affiliated to National French social security system (registered or being a beneficiary of such a scheme)
  7. Women of childbearing potential should be advised and agree to avoid becoming pregnant while receiving treatment and to use highly effective contraceptive methods at initiation of, during and at least 3 months after the last dose of treatment; pregnancy testing must be conducted prior to treatment and during treatment as appropriate; breast-feeding should be discontinued during treatment
  8. In male patients, with WOCBP partner(s), willingness to use adequate contraceptive measures to prevent his partner from becoming pregnant during the study, prior to administration of the first dose of study treatment until 3 months after the last dose of study treatment

Exclusion criteria

Exclusion Criteria:

  1. Synchronous Follicular Dendritic Cell sarcoma
  2. Known hypersensitivity to nintedanib, soy or peanut or to any of the excipients of the experimental drug, or known hypersensitivity to the auxiliary drugs listed or to any of their excipients.
  3. For women of childbearing age: negative serum or urine pregnancy test at inclusion and confirmed each month during the study, up to 3 months after the last dose.
  4. Inability to obtain informed consent
  5. Patients under legal protection
  6. Liver transaminases (AST and/or ALT) >3N
  7. End-stage liver disease (Child B or C cirrhosis)
  8. End-stage renal failure (CrCl\<30 mL/min)
  9. Severe hemorrhagic or thromboembolic events in the past 6 months
  10. Uncontrolled systemic illness such as chronic heart failure, unstable angina, hypertension; history of myocardial infarction or stroke or aneurysm
  11. Major injuries in the 10 days prior to start of the study, or Recent surgery with inadequate wound healing, or Abdominal surgery in the past 4 weeks.
  12. Severe pulmonary hypertension

  13. Bleeding risk, any of the following:

    1. Known genetic predisposition to bleeding.
    2. Patients who require
  1. Fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin) 2. High dose antiplatelet therapy corresponding to a combination of two anti-platelet aggregation treatment (aspirin + an Inhibitor of P2Y12 receptor) 14. Contraindication to the experimental drug or auxiliary drugs listed 15. Patients under guardianship or curatorship and protected adults or unable to consent 16. Enrollment in another interventional study (ongoing at the time of inclusion)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
13 participants (estimated)

Study arms

  • Experimental
    Adult patients aged 18 and over with unicentric hyalino-vascular Castleman's disease

    Drug: Nintedanib

Interventions

  • DrugNintedanib

    Nintedanib150 mg twice a day for 6 months Or Nintedanib 100mg twice a day in case of dose adjustment Oral route (during meals)

06

What researchers measure

Primary outcomes

  1. Best response

    Best response over 6 months defined as \&gt;30% decrease from baseline in Total Lesion Glycolysis (TLG) measured by 18F FDG PET/CT performed at M3 and M6

    Time frame: Up to 6 months

Secondary outcomes

  1. Number of adverse events

    Time frame: Up to 9 months

  2. Number of serious adverse events

    Time frame: Up to 9 months

  3. Nindetanib discontinuation

    Time frame: Up to 9 months

  4. Size of the lesion

    Variation from baseline

    Time frame: At 3 months

  5. Ssize of the lesion

    Variation from baseline

    Time frame: At 6 months

  6. Variation from baseline in Standardized Uptake Value of the lesion

    Time frame: At 3 months

  7. Variation from baseline in Standardized Uptake Value of the lesion

    Time frame: At 6 months

  8. Variation from baseline in Total Lesion Glycolysis (TLG) percentage of the lesion

    Time frame: At 3 months

  9. Variation from baseline in Total Lesion Glycolysis (TLG) percentage of the lesion

    Time frame: At 6 months

  10. Change in the status of non-resectability of the Unicentric Castleman Disease lesion

    Time frame: At 6 months

  11. Pemphigus disease area index (for Paraneoplastic pemphigus)

    Evolution of autoimmune-related complications by a score developped by the International Pemphigus Definitions Committee. It evaluates 3 components : skin, scalp, and mucous membranes assessing for each one activity and damage. The score varies between 0 to 263, the higher the score, he more severe the disease.

    Time frame: At 1 month

  12. Pemphigus disease area index (for Paraneoplastic pemphigus)

    Evolution of autoimmune-related complications by a score developped by the International Pemphigus Definitions Committee. It evaluates 3 components : skin, scalp, and mucous membranes assessing for each one activity and damage. The score varies between 0 to 263, the higher the score, he more severe the disease.

    Time frame: At 3 months

  13. Pemphigus disease area index (for Paraneoplastic pemphigus)

    Evolution of autoimmune-related complications by a score developped by the International Pemphigus Definitions Committee. It evaluates 3 components : skin, scalp, and mucous membranes assessing for each one activity and damage. The score varies between 0 to 263, the higher the score, he more severe the disease.

    Time frame: At 9 months

  14. For bronchiolitis obliterans : change from baseline of the percent of predicted forced expiratory volume in 1 second (FEV1)

    Evolution of autoimmune-related complications

    Time frame: At 3 months

  15. For bronchiolitis obliterans : change from baseline of the percent of predicted forced expiratory volume in 1 second (FEV1)

    Evolution of autoimmune-related complications

    Time frame: At 6 months

  16. For bronchiolitis obliterans : change from baseline of the percent of predicted forced expiratory volume in 1 second (FEV1)

    Evolution of autoimmune-related complications

    Time frame: At 9 months

  17. For bronchiolitis obliterans : change from baseline in forced vital capacityin forced vital capacity

    Evolution of autoimmune-related complications

    Time frame: At 3 months

  18. For bronchiolitis obliterans : change from baseline in forced vital capacityin forced vital capacity

    Evolution of autoimmune-related complications

    Time frame: At 6 months

  19. For bronchiolitis obliterans : change from baseline in forced vital capacityin forced vital capacity

    Evolution of autoimmune-related complications

    Time frame: At 9 months

  20. For bronchiolitis obliterans : change from baseline in total lung capacity

    Evolution of autoimmune-related complications

    Time frame: At 3 months

  21. For bronchiolitis obliterans : change from baseline in total lung capacity

    Evolution of autoimmune-related complications

    Time frame: At 6 months

  22. For bronchiolitis obliterans : change from baseline in total lung capacity

    Evolution of autoimmune-related complications

    Time frame: At 9 months

  23. For bronchiolitis obliterans : change from baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Evolution of autoimmune-related complications

    Time frame: At 3 months

  24. For bronchiolitis obliterans : change from baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Evolution of autoimmune-related complications

    Time frame: At 6 months

  25. For bronchiolitis obliterans : change from baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Evolution of autoimmune-related complications

    Time frame: At 9 months

  26. For Paraneoplastic pemphigus/Bronchiolitis Obliterans: serum antibody titers

    anti desmoglein 1/3, anti desmoplakin, anti envoplakin, anti periplakin

    Time frame: At 3 months

  27. For Paraneoplastic pemphigus/Bronchiolitis Obliterans: serum antibody titers

    anti desmoglein 1/3, anti desmoplakin, anti envoplakin, anti periplakin

    Time frame: At 6 months

  28. For Paraneoplastic pemphigus/Bronchiolitis Obliterans: serum antibody titers

    anti desmoglein 1/3, anti desmoplakin, anti envoplakin, anti periplakin

    Time frame: At 9 months

  29. For Myasthenia gravis : change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) profile score

    8 items score ranging from 0 (normal) to 24 (most severe).

    Time frame: At 1 month

  30. For Myasthenia gravis : change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) profile score

    8 items score ranging from 0 (normal) to 24 (most severe).

    Time frame: At 3 months

  31. For Myasthenia gravis : change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) profile score

    8 items score ranging from 0 (normal) to 24 (most severe).

    Time frame: At 6 months

  32. For Myasthenia gravis : change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) profile score

    8 items score ranging from 0 (normal) to 24 (most severe).

    Time frame: At 9 months

  33. For Myasthenia gravis : anti AchR/MusK titers

    Time frame: At 3 months

  34. For Myasthenia gravis : anti AchR/MusK titers

    Time frame: At 6 months

  35. For Myasthenia gravis : anti AchR/MusK titers

    Time frame: At 9 months

  36. Evaluation of the mutational status of PDGFRB (Platelet Derived Growth Factor Receptor B) of the lesion and correlation with treatment response

    Treatment response is evaluated by variation in size, SUV (Standardized Uptake Value), TLG (Total Lesion Glycolysis)

    Time frame: At 3 months

  37. Evaluation of the mutational status of PDGFRB (Platelet Derived Growth Factor Receptor B) of the lesion and correlation with treatment response

    Treatment response is evaluated by variation in size, SUV (Standardized Uptake Value) , TLG (Total Lesion Glycolysis)

    Time frame: At 6 months

  38. Nintedanib residual plasma concentration

    Time frame: At 1 month

  39. Nintedanib residual plasma concentration

    Time frame: At 3 months

  40. Nintedanib residual plasma concentration

    Time frame: At 6 months

07

Study locations

No study locations are listed for this record.

08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 15, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06643091
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Oct 15, 2024
Start date
Nov 1, 2024 (estimated)
Primary completion
May 1, 2030 (estimated)
Completion
Sep 1, 2030 (estimated)
Last update
Oct 15, 2024

Study contacts

David Boutboul, MD
Contact
david.boutboul@aphp.fr
+33142499140 ext. +33
Jérôme Lambert, MD PhD
Contact
jerome.lambert@u-paris.fr
+33142499742 ext. +33

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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