A Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Steroid Dependent/Refractory Chronic Graft Versus Host Disease (cGVHD)
Study Details
Study Description
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]).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
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:
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Outcome Measures
Primary Outcome Measures
- Percentage of Participants who Achieve Complete Response (CR) or Partial Response (PR) (i.e. Overall Response Rate [ORR]) [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.
Secondary Outcome Measures
- Percentage of Participants with Sustained Response [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) [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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 [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).
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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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
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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
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Clinically stable or worsening cGVHD for a minimum of 14 days between screening and Day 1 cGVHD response assessment
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Karnofsky or Lansky (participants less than [<]16 years) performance status >=60
Exclusion Criteria:
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Active acute graft versus host disease (GVHD)
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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
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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
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History of treatment with monoclonal T and B cell antibodies in the 8 weeks prior to starting ibrutinib
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Vaccinated with live, attenuated vaccines within 4 weeks of first dose of ibrutinib
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anjo Kosei Hospital | Anjo-shi | Japan | 446-8602 | |
| 2 | Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital | Bunkyo-ku | Japan | 113-8677 | |
| 3 | Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital | Hiroshima | Japan | 730-8619 | |
| 4 | Kobe City Medical Center General Hospital | Hyogo | Japan | 650-0047 | |
| 5 | Tokai University Hospital | Isehara | Japan | 259-1193 | |
| 6 | Osaka Women's and Children's Hospital | Izumi | Japan | 594-1101 | |
| 7 | National Hospital Organization Kumamoto Medical Center | Kumamoto | Japan | 860-0008 | |
| 8 | Kurashiki Central Hospital | Kurashiki | Japan | 710-8602 | |
| 9 | Gunmaken Saiseikai Maebashi Hospital | Maebashi | Japan | 371-0821 | |
| 10 | Japanese Red Cross Nagoya Daiichi Hospital | Nagoya | Japan | 453-8511 | |
| 11 | The Hospital of Hyogo College of Medicine | Nishinomiya | Japan | 663-8501 | |
| 12 | Okayama University Hospital | Okayama | Japan | 700-8558 | |
| 13 | Osaka City University Hospital | Osaka | Japan | 545-8586 | |
| 14 | Hokkaido University Hospital | Sapporo-shi | Japan | 060-8648 | |
| 15 | National Center for Child Health and Development | Setagaya-ku | Japan | 157-8535 |
Sponsors and Collaborators
- Janssen Pharmaceutical K.K.
Investigators
- Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial, Janssen Pharmaceutical K.K.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR108443
- 54179060GVH3001