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

NCT03790332 | Completed Phase 1 FDA Drug

• 2 other identifiers: PCYC-1146-IM2017-004558-41
• Study Type: interventional
• Target: 59
• Locations: 12 countries
• Sites: 47

Brief Summary

Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects with Chronic Graft Versus Host Disease (cGVHD)

Conditions

Chronic Graft Versus Host Disease

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• 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

Study Arms (1)

Phase 1/2

EXPERIMENTAL

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

Interventions

Ibrutinib DRUG

Ibrutinib capsule, tablet, or suspension administered orally once daily

Also known as: IMBRUVICA®, PCI-32765

Phase 1/2

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:

You may not qualify if:

• 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)

Sponsors & Collaborators

• Pharmacyclics LLC.: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (48)

City of Hope

Duarte, California, 91010, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of California

San Francisco, California, 94158, United States

Location

Children's Hospital

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Ann & Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, 55454, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105-2729, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cancer Center for Children. The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Sydney Children's Hospital

Randwick, 2031, Australia

Location

St. Anna Kinderspital

Vienna, 1090, Austria

Location

children's and Women's Health Centre of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CHU Sainte-Justine

Montreal, Quebec, H3T1C5, Canada

Location

CHU Nantes - Hopital Enfant Adolescent

Nantes, 44093, France

Location

Hôpital Robert-Debré Ap-Hp

Paris, 75019, France

Location

Charite-Universitaetsmedizin Berlin

Berlin, 13353, Germany

Location

Hadassah Medical Centre

Jerusalem, 9112001, Israel

Location

Schneider Children's Medical Center in Israel

Petah Tikva, 4920235, Israel

Location

The Edmond and Lily Safra Children's Hospital

Ramat Gan, 5262100, Israel

Location

U.O.C. Ematologia Oncoematologia Pediatrica

Pavia, PV, 27100, Italy

Location

Fondazione MBBM-Clinica Pediatrica

Monza, 20900, Italy

Location

Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica

Roma, 00165, Italy

Location

S.C. Farmacia Pediatrica - Presidio Ospedaliero Infantile Regina Margherita

Turin, 10126, Italy

Location

Princess Maxima Center

Utrecht, 3584 CS, Netherlands

Location

Federal State Budgetary Institution "Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Moscow, 117997, Russia

Location

Federal State Budgetary Educational Institution of Higher Professional Education "LP.Pavlov First Saint Petersburg State Medical

Saint Petersburg, 197022, Russia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul Saint Mary's Hospital

Seoul, 06591, South Korea

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Hospital Universitario Universitario La Paz

Madrid, 28046, Spain

Location

Safari Day Care, Great Ormond Street Hospital

London, Greater London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Study Officials

• Gauri Sunkersett

  Pharmacyclics LLC.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2018
• First Posted: December 31, 2018
• Study Start: November 19, 2018
• Primary Completion: October 9, 2025
• Study Completion: October 9, 2025
• Last Updated: October 21, 2025

Record last verified: 2025-05

Locations

NL (1); GB (1); AU (4); DE (1); FR (2); IL (3); CA (2); IT (4); US (20); RU (2); KR (4); ES (3)