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

Phase 1

Active, not recruiting

• Conditions: Chronic Graft Versus Host Disease
• Interventions: Drug: Ibrutinib

• 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

Study Timeline

• Study Start: 2018-11-19
• Study First Submitted: 2018-12-12
• Study First Submitted QC: 2018-12-27
• Study First Posted: 2018-12-31
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-27
• Last Update Posted: 2025-05-31
• Primary Completion: 2026-01-04
• Study Completion: 2026-01-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 59

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

3. History of allogeneic stem cell transplantation

4. 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

5. Karnofsky or Lansky (subjects <16 years of age) performance status ≥60

Key Eligibility:

Exclusion Criteria

1. Presence of single organ genito-urinary involvement as the only manifestation of cGVHD
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. Any uncontrolled infection or active infection requiring ongoing systemic treatment
6. Known bleeding disorders
7. 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)

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 Hospital; 🇺🇸 Aurora, Colorado, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Johns Hopkins All Children's Hospital; 🇺🇸 Saint Petersburg, Florida, United States

Ann & Robert H Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

University of Minnesota Masonic Children's Hospital; 🇺🇸 Minneapolis, Minnesota, United States

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