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
- Interventions
- Registration Number
- NCT03790332
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 59
-
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:
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1/2 Ibrutinib 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.
- Primary Outcome Measures
Name Time Method Number of patients with adverse events as a measure of safety and tolerability Approximately 7 years 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
- Secondary Outcome Measures
Name Time Method 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 Growth Parameter weight in kilograms will be reported descriptively. Up to 5 years post enrollment Subjects will be monitored for growth and development
Available immune reconstitution laboratory parameters will be reported descriptively Up to 5 years post enrollment Subjects will be monitored for immune reconstitution
Late effects (Adverse events suspected to be related to treatment) will be quantified and reported descriptively Up to 5 years post enrollment Growth Parameter height in meters will be reported descriptively Up to 5 years post enrollment Subjects will be monitored for growth and development
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-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
Trial Locations
- Locations (48)
Ann & Robert H Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Hôpital Robert-Debré Ap-Hp
🇫🇷Paris, France
The Edmond and Lily Safra Children's Hospital
🇮🇱Ramat Gan, Israel
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Queensland Children's Hospital
🇦🇺South Brisbane, Queensland, Australia
Children's Hospital
🇺🇸Aurora, Colorado, United States
University of Minnesota Masonic Children's Hospital
🇺🇸Minneapolis, Minnesota, United States
City of Hope
🇺🇸Duarte, California, United States
Rady Children's Hospital
🇺🇸San Diego, California, United States
University of California
🇺🇸San Francisco, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Sydney Children's Hospital
🇦🇺Randwick, Australia
The Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Cancer Center for Children. The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
St. Anna Kinderspital
🇦🇹Wien, Austria
children's and Women's Health Centre of British Columbia
🇨🇦Vancouver, British Columbia, Canada
CHU Sainte-Justine
🇨🇦Montréal, Quebec, Canada
CHU Nantes - Hopital Enfant Adolescent
🇫🇷Nantes, France
Schneider Children's Medical Center in Israel
🇮🇱Petach Tikva, Israel
Charite-Universitaetsmedizin Berlin
🇩🇪Berlin, Germany
Hadassah Medical Centre
🇮🇱Jerusalem, Israel
U.O.C. Ematologia Oncoematologia Pediatrica
🇮🇹Pavia, PV, Italy
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
🇮🇹Roma, Italy
Fondazione MBBM-Clinica Pediatrica
🇮🇹Monza, Italy
S.C. Farmacia Pediatrica - Presidio Ospedaliero Infantile Regina Margherita
🇮🇹Turin, Italy
Princess Maxima Center
🇳🇱Utrecht, Netherlands
Federal State Budgetary Educational Institution of Higher Professional Education "LP.Pavlov First Saint Petersburg State Medical
🇷🇺Saint Petersburg, Russian Federation
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Federal State Budgetary Institution "Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
🇷🇺Moscow, Russian Federation
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Safari Day Care, Great Ormond Street Hospital
🇬🇧London, Greater London, United Kingdom
Hospital Universitario Universitario La Paz
🇪🇸Madrid, Spain
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain