AzTrials
AzTrials

Castleman DiseasePhase 2NUCastleNCT06643091

Nintedanib Treatment in Unicentric Castleman Disease

A Phase 2 study testing Nintedanib in people with Castleman Disease, run by Assistance Publique - Hôpitaux de Paris.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Castleman Disease
What is being tested?
Nintedanib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
No sites listed yet
Study dates
1 Nov 2024to 1 Sep 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ (equal to or greater than) 18 years
  • Written informed consent
  • Biopsy-proven diagnosis of hyaline-vascular Unicentric Castleman disease
  • Unresectable or partially resectable UCD lesion or surgery refusal
  • Available oral route
  • Affiliated to National French social security system (registered or being a beneficiary of such a scheme)
  • 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
  • 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

Who cannot join

  • Synchronous Follicular Dendritic Cell sarcoma
  • 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.
  • 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.
  • Inability to obtain informed consent
  • Patients under legal protection
  • Liver transaminases (AST and/or ALT) \>3N
Show all 16Show fewer
  • End-stage liver disease (Child B or C cirrhosis)
  • End-stage renal failure (CrCl\<30 mL/min)
  • Severe hemorrhagic or thromboembolic events in the past 6 months
  • Uncontrolled systemic illness such as chronic heart failure, unstable angina, hypertension; history of myocardial infarction or stroke or aneurysm
  • 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.
  • Severe pulmonary hypertension
  • Bleeding risk, any of the following:
  • Known genetic predisposition to bleeding.
  • 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)

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

David Boutboul, MD contact

+33142499140 ext. +33

david.boutboul@aphp.fr

Jérôme Lambert, MD PhD contact

+33142499742 ext. +33

jerome.lambert@u-paris.fr

About this study

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.

Being tested
Nintedanib
Keywords
Castleman disease
Medical subject headings
Castleman Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NintedanibDrug

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

Study groups in NCT06643091
Study groupRoleWhat they receive
Adult patients aged 18 and over with unicentric hyalino-vascular Castleman's diseaseExperimentalNot described
Receives: Drug: Nintedanib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best response

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

    Measured: Up to 6 months

Secondary outcomes (40)

  1. Number of adverse events

    Measured: Up to 9 months

  2. Number of serious adverse events

    Measured: Up to 9 months

  3. Nindetanib discontinuation

    Measured: Up to 9 months

  4. Size of the lesion

    Variation from baseline

    Measured: At 3 months

  5. Ssize of the lesion

    Variation from baseline

    Measured: At 6 months

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

    Measured: At 3 months

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

    Measured: At 6 months

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

    Measured: At 3 months

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

    Measured: At 6 months

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

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: At 9 months

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

    Evolution of autoimmune-related complications

    Measured: At 3 months

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

    Evolution of autoimmune-related complications

    Measured: At 6 months

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

    Evolution of autoimmune-related complications

    Measured: At 9 months

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

    Evolution of autoimmune-related complications

    Measured: At 3 months

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

    Evolution of autoimmune-related complications

    Measured: At 6 months

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

    Evolution of autoimmune-related complications

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: At 9 months

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

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

    Measured: At 3 months

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

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

    Measured: At 6 months

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

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

    Measured: 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).

    Measured: 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).

    Measured: 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).

    Measured: 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).

    Measured: At 9 months

  33. For Myasthenia gravis : anti AchR/MusK titers

    Measured: At 3 months

  34. For Myasthenia gravis : anti AchR/MusK titers

    Measured: At 6 months

  35. For Myasthenia gravis : anti AchR/MusK titers

    Measured: 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)

    Measured: 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)

    Measured: At 6 months

  38. Nintedanib residual plasma concentration

    Measured: At 1 month

  39. Nintedanib residual plasma concentration

    Measured: At 3 months

  40. Nintedanib residual plasma concentration

    Measured: At 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Oct 2024
  2. Study start1 Nov 2024 (estimated)
  3. Primary completion1 May 2030 (estimated)
  4. Study completion1 Sep 2030 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Model description
Multicenter open label and single-arm phase II trial
Masking
None (open label)
Enrolment
13 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06643091
Sponsor's protocol ID
APHP230820
Acronym
NUCastle
Status last verified
Sep 2024
First submitted
13 Sep 2024
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nintedanib in people with Castleman Disease, run by Assistance Publique - Hôpitaux de Paris.

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 8 inclusion and 16 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: opening soon, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact David Boutboul, MD (+33142499140 ext. +33, david.boutboul@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Best response (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06643091.

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 15 Oct 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in