A Study to Investigate the Comparative Effectiveness of Ibrutinib in Steroid Dependent/Refractory cGVHD Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of ibrutinib compared to conventional salvage treatments in participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) by measuring overall cGVHD response (modified National Institutes of Health [NIH] response defined complete response [CR] and partial response [PR]) at Week 24.

Official Title
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A Retrospective/Prospective, Multicenter, Non-interventional, Historical Control Study Investigating Comparative Effectiveness of IMBRUVICA in Steroid Dependent/Refractory cGVHD Patients

Conditions
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Chronic Graft vs Host Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Part A and Part B Must have a confirmed diagnosis of steroid dependent or refractory classic cGVHD defined at any time post-hematopoietic cell transplantation (HCT) as: a) refractory disease - progressive cGVHD manifestations requiring prednisolone at greater than or equal to (>=) 1 milligram per kilogram per day (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; b) dependent disease: persistent cGVHD manifestations requiring glucocorticoid >= prednisolone 0.25 mg/kg/day or >=0.5mg/kg every other day for at least 8 weeks Part A Treated at least 2 or more therapies for cGVHD (including glucocorticoids) Participants whose identified last line of conventional salvage treatment is second-fourth line of therapy Index date (initiation date of the identified last-line of conventional salvage therapy) at least 28 weeks before the study initiation date Part B Treated at least 3 lines therapies for cGVHD (including glucocorticoids) Participants who are treated with ibrutinib in their second-fourth line of therapy Exclusion Criteria: Part A and Part B Known or suspected active acute GVHD Received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 28 days Part A Treated with an investigational agent for their identified last-line of conventional salvage therapy Pregnant, breastfeeding during last-line of conventional salvage therapy Part B Pregnant, breast-feeding, or of childbearing potential without a negative serum or urine pregnancy test within 7 days of enrollment. Male or female participants of childbearing potential unwilling to use effective contraceptive precautions throughout the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Part A: Retrospective Phase<br>Retrospective collection of data for eligible participants with steroid dependent/refractory chronic graft versus host disease (cGVHD) who initiated salvage treatments from initiation point (administration starting point of the salvage treatment) of the identified last-line of conventional salvage therapy for cGVHD treatment as their second-forth line therapy and will be collected for up to 24 weeks from the initiation point. | |
| Part B: Prospective Phase<br>Prospectively enroll participants with steroid dependent/refractory cGVHD that are decided to be treated with ibrutinib in second-fourth line therapy for the treatment of cGVHD. Participants will continue to receive corticosteroids as a standard of care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A and Part B: Percentage of Participants with Overall Response Rate | Overall response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) according to modified National Institutes of Health (NIH) response. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Rate of Sustained Response | Sustained response rate will be assessed. | At least 5 months (up to 36 weeks) | 
| Part B: Duration of Response | Duration of response will be assessed. | Up to 5 months | 
| Part A and Part B: Corticosteroid Requirement Changes Over Time | The change of the corticosteroid dose requirement during the treatment will be assessed. | Up to 24 weeks | 
| Part B: Time to cGVHD Progression | Time to chronic graft versus host disease (cGVHD) progression is defined as the time from the first dose of the ibrutinib to modified NIH response defined progression. | Up to 36 weeks | 
| Part B: Change in Lee cGVHD Symptom Scale | Change in Lee cGVHD symptom scale will be assessed. It is a participant reported improvement in symptom burden. | Up to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic, Ibrutinib, Retrospective, Prospective