Chronic Graft Versus Host Disease (cGVHD) MedDRA version: 20.1 Level: PT Classification code 10066261 Term: Chronic graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: Ibrutinib, 70mg capsules
Product Code: PCI-32765
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Num
Sponsors
Pharmacyclics LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Part A: Subjects with moderate or severe cGVHD after failure of 1 or more lines of systemic therapy 2. 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. a. Subjects with new onset moderate or severe cGVHD must not have received previous systemic therapy for cGVHD with the exception of corticosteroids received within 72 hours prior to signing the informed consent form. b. Subjects with newly diagnosed cGVHD may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD, but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d at the time of enrollment. 3. History of allogeneic stem cell transplantation 4. Age • Part A: =1 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Presence of single organ genito-urinary involvement as the only manifestation of cGVHD. Concurrent Conditions 2. Received an investigational agent within 28 days before enrollment. 3. Received donor lymphocyte infusion (DLI) within 56 days before enrollment. 4. Progressive underlying malignant disease or active post-transplant lymphoproliferative disease. 5. Ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonist. 6. History of other malignancy (not including the underlying malignancy that was the indication for transplant), with the following exceptions: • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to enrollment and felt to be at low risk for recurrence by treating physician • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease • Adequately treated cervical carcinoma in situ without current evidence of disease 7. History of major surgery within 28 days before enrollment or lack of full recovery from surgery. 8. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk. 9. Female subject who is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months of the last dose of study drug. Male subject who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug. 10. Unwilling or unable to participate in all required study evaluations and procedures.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: The secondary endpoints are safety, including treatment-emergent AEs, laboratory abnormalities, and other safety endpoints; pharmacodynamics (BTK occupancy) and for those subjects continuing therapy after dose escalation (Part A Continuation Cohort), secondary endpoints will be the same as outlined under Part B below. Part B: The secondary endpoints include cGVHD response rate (i.e. the proportion of responders [CR or PR]) at 24 weeks; duration of response; overall survival rate; growth and development in pediatric subjects (i.e., height, weight, Tanner Stage, and head circumference in subjects < 3years), and immune reconstitution data ;Timepoint(s) of evaluation of this end point: After all subjects have had the opportunity to complete 24 weeks of treatment. | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A - Dose Finding Study Primary Objective: To determine the RPED (based on PK and, if applicable, pharmacodynamic data) for use in pediatric subjects (age =1 to <12 years) with cGVHD as defined by the 2014 NIH Consensus Development Project Criteria. Part B - Pharmacokinetics, Safety, and Efficacy Study Primary Objective: To assess the PK and safety and efficacy of ibrutinib in pediatric subjects (age = 1 to < 22 years) with cGVHD. ; Secondary Objective: Part A - Dose Finding Study • To determine the safety of ibrutinib in pediatric subjects with cGVHD • To assess pharmacodynamics (BTK occupancy) of ibrutinib in pediatric subjects with cGVHD • For those subjects continuing therapy after dose escalation (Part A Continuation Cohort), secondary endpoints will be the same as those outlined under Part B below and will include safety and efficacy Part B - Pharmacokinetics, Safety, and Efficacy Study • To evaluate the efficacy of ibrutinib treatment at 24 weeks in pediatric subjects with cGVHD using the 2014 NIH Consensus Development Project Criteria • To evaluate the duration of response to ibrutinib treatment in pediatric subjects with cGVHD • To evaluate the overall survival rate in pediatric subjects with cGVHD treated with ibrutinib • To evaluate safety by assessing the potential impact of ibrutinib on late effects (including effects on growth and development and immune reconstitution) in pediatric subjects with GVHD ; Primary end point(s): Part A: The primary endpoint is the PK (AUC) to determine the RPED of ibrutinib for use in pediatric subjects (age = 1 to < 12 years) with cGVHD. Part B: The primary endpoint is the PK (AUC) and safety (treatment-emergent AEs and laborato | — |
Countries
Australia, Austria, Canada, France, Germany, Italy, Netherlands, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactClinical Operations
Pharmacyclics LLC
Outcome results
None listed