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A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

30. Dezember 2021 aktualisiert von: Janssen Pharmaceutical K.K.

A Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Subjects With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)

The purpose of this study is to evaluate efficacy of ibrutinib in Japanese participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (complete response [CR] and partial response [PR] defined by National Institutes of Health [NIH] consensus development project criteria [2014]).

Studienübersicht

Status

Abgeschlossen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Tatsächlich)

19

Phase

  • Phase 3

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

      • Anjo-shi, Japan, 446-8602
        • Anjo Kosei Hospital
      • Bunkyo-ku, Japan, 113-8677
        • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
      • Hiroshima, Japan, 730-8619
        • Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital
      • Hyogo, Japan, 650-0047
        • Kobe City Medical Center General Hospital
      • Isehara, Japan, 259-1193
        • Tokai University Hospital
      • Izumi, Japan, 594-1101
        • Osaka Women's and Children's Hospital
      • Kumamoto, Japan, 860-0008
        • National Hospital Organization Kumamoto Medical Center
      • Kurashiki, Japan, 710-8602
        • Kurashiki Central Hospital
      • Maebashi, Japan, 371-0821
        • Gunmaken Saiseikai Maebashi Hospital
      • Nagoya, Japan, 453-8511
        • Japanese Red Cross Nagoya Daiichi Hospital
      • Nishinomiya, Japan, 663-8501
        • The Hospital of Hyogo College of Medicine
      • Okayama, Japan, 700-8558
        • Okayama University Hospital
      • Osaka, Japan, 545-8586
        • Osaka City University Hospital
      • Sapporo-shi, Japan, 060-8648
        • Hokkaido University Hospital
      • Setagaya-ku, Japan, 157-8535
        • National Center for Child Health and Development

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

12 Jahre und älter (Kind, Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Steroid dependent/refractory chronic graft versus host disease (cGVHD) defined as modified National Institutes of Health (NIH) criteria (2014) below at any time post-hematopoietic cell transplant (post-HCT): a) Dependent disease, defined as, when glucocorticoid (prednisolone doses greater than or equal to [>=] 0.25 milligram per kilogram per day (mg/kg/day)or >=0.5 milligram per kilogram (mg/kg) every other day) are needed to prevent recurrence or progression of manifestations as demonstrated by unsuccessful attempts to taper the dose to lower levels on at least 2 occasions, separated by at least 8 weeks. In case of inability to taper the dose to less than or equal to (<=)0.25 mg/kg/day or <=0.5 mg/kg every other day (prednisolone doses) due to recurrence or progression of cGVHD manifestations, it is considered as steroid-dependent disease if the lowest tapering dose of the second occasion is equal or higher than the lowest tapering dose of the first occasion; b) Refractory disease, defined as, when cGVHD manifestations progress despite the use of a regimen containing glucocorticoid (prednisolone at >=1 mg/kg/day for at least 1 week) or persist without improvement despite continued treatment with glucocorticoid (prednisolone at >=0.5 mg/kg/day or 1 mg/kg every other day) for at least 4 weeks
  • Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting ibrutinib
  • At the time of trial enrollment, participants may be receiving other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting ibrutinib
  • Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
  • Karnofsky or Lansky (participants less than [<]16 years) performance status >=60

Exclusion Criteria:

  • Active acute graft versus host disease (GVHD)
  • More than 3 previous systemic treatments for cGVHD. Treatment with glucocorticoids is considered a treatment for cGVHD and should be included in determining the number of previous treatments
  • History of treatment with a tyrosine kinase inhibitor (example [e.g.] imatinib), purine analogs, or other cancer chemotherapy in the 4 weeks prior to starting ibrutinib. Participants may have received ibrutinib pre-transplant for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma
  • History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: N / A
  • Interventionsmodell: Einzelgruppenzuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: Ibrutinib
Participants will receive 420 milligram (mg) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Participants will receive 420 mg (3 * 140 mg capsules) oral ibrutinib once daily starting on Week 1 Day 1, unless they have intervening unacceptable toxicity or meet other criteria for participants discontinuation.
Andere Namen:
  • PCI-32765
  • JNJ-54179060

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR])
Zeitfenster: Approximately up to 4.5 years
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR). Response is defined by the National Institutes of Health (NIH) Consensus Development Project Criteria (2014) and must occur, in the absence of new therapy for chronic graft versus host disease (cGVHD) and absence of progression of underlying disease or death. CR: Resolution of all manifestations in each organ or site. PR: Improvement in at least 1 organ or site without progression in any other organ or site. cGVHD Progression: Clinically meaningful worsening in 1 or more organs regardless of improvement in other organs.
Approximately up to 4.5 years

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Percentage of Participants with Sustained Response
Zeitfenster: Approximately up to 4.5 years
Percentage of participants with sustained response is defined as rate of NIH defined CR or PR that was sustained for at least 20 weeks.
Approximately up to 4.5 years
Duration of Response (DOR)
Zeitfenster: From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
DOR is defined as the duration of time from the date of initial response (CR or PR) to the date of progressive cGVHD or death, whichever occurs first.
From the date of initial documentation of a response to the date of first documented evidence of progressive cGVHD or death, whichever occurs first (approximately up to 4.5 years)
Percentage of Participants with cGVHD response at Each Timepoint of Efficacy Evaluation
Zeitfenster: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Percentage of Participants with cGVHD response at each timepoint of efficacy evaluation (cGVHD response rate) is defined as percentage of participants with NIH defined CR or PR at each timepoint.
Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and every 12 weeks (q12w) thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Change in the Amount of Corticosteroid Required Per Participant Over Time
Zeitfenster: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Change in the amount of corticosteroid required per participant over time will be monitored across the study.
Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Improvement in Symptom Burden Measured by the Lee cGVHD Symptom Scale
Zeitfenster: Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Lee cGVHD Symptom Scale is a participant-reported symptom scale. It includes a total of 30 items within the following 7 domains: Skin, eyes and mouth, breathing, eating and digestion, muscles and joints, energy, mental and emotional for evaluating overall response. Response options range from 0 to 4 and includes: "not at all" (0), "Slightly" (1), "Moderately" (2), "Quite a bit" (3), and "extremely" (4), and yield an overall score. A change greater than or equal to (>=) 7 points on the Lee cGVHD Symptom Scale will be considered significant and relates to improvement in quality of life (QoL).
Screening, Day 1 Weeks 1, 5, 13 and 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment and Response Follow-up Visits (until progressive cGVHD) q12w (approximately up to 4.5 years)
Number of Participants with Adverse Events (AEs) as a Measure of Safety
Zeitfenster: From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
From signing Informed Consent Form until 30 days after the last dose of study treatment (approximately up to 4.5 years)
Number of Participants with Clinical Laboratory Abnormalities
Zeitfenster: Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
Number of participants with clinical laboratory abnormalities will be reported.
Screening, Day 1 Weeks 1, 2, 5, 9, 13, 17, 21, 25, Week 37 and q12w thereafter, Progressive cGVHD Visit, End-of-Treatment (approximately up to 4.5 years)
Area Under the Plasma Concentration-Time Curve from Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax is defined as the maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination Half-Life (t1/2) of Ibrutinib
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) of Metabolite PCI-45227
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-last) is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) of Metabolite PCI-45227
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
AUC (0-24) is defined as the area under the plasma concentration-time curve from time zero to 24 hours.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax of Metabolite PCI-45227
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Cmax is defined as the maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax of Metabolite PCI-45227
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
t1/2 of Metabolite PCI-45227
Zeitfenster: Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1
Elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Day 1 (Predose, 1 hour [h], 2h, 4h, 6h) Weeks 1 and 2; Day 2 (Predose) Week 1

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

1. Mai 2018

Primärer Abschluss (Tatsächlich)

29. November 2021

Studienabschluss (Tatsächlich)

29. November 2021

Studienanmeldedaten

Zuerst eingereicht

16. März 2018

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

16. März 2018

Zuerst gepostet (Tatsächlich)

22. März 2018

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

3. Januar 2022

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

30. Dezember 2021

Zuletzt verifiziert

1. Dezember 2021

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • CR108443
  • 54179060GVH3001 (Andere Kennung: Janssen Pharmaceutical K.K., Japan)

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Ja

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

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