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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03474679
Recruitment Status : Active, not recruiting
First Posted : March 22, 2018
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.

Tracking Information
First Submitted Date  ICMJE March 16, 2018
First Posted Date  ICMJE March 22, 2018
Last Update Posted Date October 17, 2019
Actual Study Start Date  ICMJE May 1, 2018
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2018)
Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR]) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03474679 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2018)
  • Percentage of Participants with Sustained Response [ Time Frame: 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.
  • Duration of Response (DOR) [ Time Frame: 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.
  • Percentage of Participants with cGVHD response at Each Timepoint of Efficacy Evaluation [ Time Frame: 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.
  • Change in the Amount of Corticosteroid Required Per Participant Over Time [ Time Frame: 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.
  • Improvement in Symptom Burden Measured by the Lee cGVHD Symptom Scale [ Time Frame: 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).
  • Number of Participants with Adverse Events (AEs) as a Measure of Safety [ Time Frame: 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.
  • Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: 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.
  • Area Under the Plasma Concentration-Time Curve from Time Zero to Time of Last Measurable Concentration (AUC [0-last]) of Ibrutinib [ Time Frame: 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.
  • Area Under the Plasma Concentration-Time Curve from Time Zero to 24 Hours (AUC [0-24]) of Ibrutinib [ Time Frame: 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.
  • Maximum Observed Plasma Concentration (Cmax) of Ibrutinib [ Time Frame: 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.
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ibrutinib [ Time Frame: 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.
  • Elimination Half-Life (t1/2) of Ibrutinib [ Time Frame: 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).
  • AUC (0-last) of Metabolite PCI-45227 [ Time Frame: 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.
  • AUC (0-24) of Metabolite PCI-45227 [ Time Frame: 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.
  • Cmax of Metabolite PCI-45227 [ Time Frame: 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.
  • Tmax of Metabolite PCI-45227 [ Time Frame: 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.
  • t1/2 of Metabolite PCI-45227 [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)
Official Title  ICMJE 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)
Brief Summary 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]).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Graft vs Host Disease
Intervention  ICMJE Drug: Ibrutinib
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.
Other Names:
  • PCI-32765
  • JNJ-54179060
Study Arms  ICMJE 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.
Intervention: Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 28, 2019)
19
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2018)
17
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date February 28, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03474679
Other Study ID Numbers  ICMJE CR108443
54179060GVH3001 ( Other Identifier: Janssen Pharmaceutical K.K., Japan )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Pharmaceutical K.K.
Study Sponsor  ICMJE Janssen Pharmaceutical K.K.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
PRS Account Janssen Pharmaceutical K.K.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP