Phase 1/2 Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects With Chronic Graft Versus Host Disease (cGVHD)

Study Overview
=================
Brief Summary
-----------------
Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)

Official Title
-----------------
Phase 1/2 Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects With Chronic Graft Versus Host Disease (cGVHD)

Conditions
-----------------
Chronic Graft Versus Host Disease

Intervention / Treatment
-----------------
* Drug: Ibrutinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Eligibility: Inclusion Criteria: Part A: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy Part B: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, or subjects with new onset moderate or severe cGVHD and in need of systemic immunosuppression History of allogeneic stem cell transplantation Age Part A: ≥1 to <12 years of age at the time of enrollment Part B: ≥1 to <22 years of age at the time of enrollment Karnofsky or Lansky (subjects <16 years of age) performance status ≥60 Key Eligibility: Exclusion Criteria: Presence of single organ genito-urinary involvement as the only manifestation of cGVHD Received an investigational agent within 28 days before enrollment. Received donor lymphocyte infusion (DLI) within 56 days before enrollment Progressive underlying malignant disease or active post-transplant lymphoproliferative disease Any uncontrolled infection or active infection requiring ongoing systemic treatment Known bleeding disorders Active hepatitis C virus (HCV) or hepatitis B virus (HBV)

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1/2<br>Part A: Subjects ≥1 to <12 years of age with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy, will receive oral ibrutinib once daily to determine Recommended Pediatric Equivalent Dose (RPED). Part A Continuation: Subjects participating in Part A may continue receiving daily ibrutinib until the RPED is determined, at which time their dose may be adjusted to the RPED. Part B: Subjects ≥1 to <12 years of age( upper age limit is < 22 years) with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy or with newly diagnosed moderate or severe cGVHD will be dosed at the RPED. Subjects ≥12 will be given 420mg orally ibrutinib once daily. | Drug: Ibrutinib<br>* Ibrutinib capsule, tablet, or suspension administered orally once daily<br>* Other names: PCI-32765;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A- PK (measured by AUC) will be reported descriptively |  | Approximately 24 months | 
| Part B- PK (measured by AUC) will be reported descriptively |  | Approximately 7 years | 
| Number of patients with adverse events as a measure of safety and tolerability |  | Approximately 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A- Number of patients with adverse events as a measure of safety and tolerability |  | Approximately 24 months | 
| Part A- Pharmacodynamic effects as measured by in vitro BTK occupancy will be reported descriptively |  | Approximately 24 months | 
| Part A continuation cohort and Part B-Response rate at 24 weeks |  | Approximately 6 months after last subject in enrolled | 
| Part A continuation cohort and Part B- Duration of response (DOR) |  | Up to 48 weeks | 
| Part A continuation cohort and Part B-Overall survival (OS) |  | Approximately 5 years after last subject enrolled | 
| Part A continuation cohort and Part B-Late Effects Surveillance |  | Up to 5 years post enrollment | 
| Growth Parameter height in meters will be reported descriptively | Subjects will be monitored for growth and development | Up to 5 years post enrollment | 
| Growth Parameter weight in kilograms will be reported descriptively. | Subjects will be monitored for growth and development | Up to 5 years post enrollment | 
| Available immune reconstitution laboratory parameters will be reported descriptively | Subjects will be monitored for immune reconstitution | Up to 5 years post enrollment | 
| Late effects (Adverse events suspected to be related to treatment) will be quantified and reported descriptively |  | Up to 5 years post enrollment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cGVHD, chronic graft versus host disease, PCYC1146IM, Pediatric, GVHD, chronic, 1146, Pharmacyclics, PCYC, Imbruvica, Ibrutinib, Immunology, graft versus host disease, corticosteroids, prednisone, PCI32765, PCYC1146, refractory, new onset graft versus host disease, refractory graft versus host disease, moderate cGVHD, severe cGVHD, moderate chronic graft versus host disease, severe chronic graft versus host disease