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

Sponsor

Pharmacyclics LLC. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03790332

Collaborator

Janssen Research & Development, LLC (Industry)

Enrollment

Locations

Arm

85.5

Anticipated Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft Versus Host Disease	Drug: Ibrutinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 19, 2018

Anticipated Primary Completion Date :

Jan 4, 2026

Anticipated Study Completion Date :

Jan 4, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1/2 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 Ibrutinib capsule, tablet, or suspension administered orally once daily Other Names: IMBRUVICA® PCI-32765

Arm

Intervention/Treatment

Experimental: Phase 1/2

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

Ibrutinib capsule, tablet, or suspension administered orally once daily

Other Names:

IMBRUVICA®

PCI-32765

Outcome Measures

Primary Outcome Measures

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

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 [Up to 5 years post enrollment]
Subjects will be monitored for growth and development
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Rady Children's Hospital	San Diego	California	United States	92123
3	University of California	San Francisco	California	United States	94158
4	Children's Hospital	Aurora	Colorado	United States	80045
5	Children's National Medical Center	Washington	District of Columbia	United States	20010
6	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
7	Ann & Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
8	Johns Hopkins University	Baltimore	Maryland	United States	21287
9	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
10	University of Minnesota Masonic Children's Hospital	Minneapolis	Minnesota	United States	55454
11	Washington University	Saint Louis	Missouri	United States	63110
12	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
13	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
14	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
15	Oregon Health and Science University	Portland	Oregon	United States	97239
16	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
17	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2729
18	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
19	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
20	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
21	Cancer Center for Children. The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
22	Queensland Children's Hospital	South Brisbane	Queensland	Australia	4101
23	The Royal Children's Hospital	Parkville	Victoria	Australia	3052
24	Sydney Children's Hospital	Randwick		Australia	2031
25	St. Anna Kinderspital	Wien		Austria	1090
26	children's and Women's Health Centre of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
27	CHU Sainte-Justine	Montréal	Quebec	Canada	H3T1C5
28	CHU Nantes - Hopital Enfant Adolescent	Nantes		France	44093
29	Hôpital Robert-Debré Ap-Hp	Paris		France	75019
30	Charite-Universitaetsmedizin Berlin	Berlin		Germany	13353
31	Hadassah Medical Centre	Jerusalem		Israel	9112001
32	Schneider Children's Medical Center in Israel	Petach Tikva		Israel	4920235
33	The Edmond and Lily Safra Children's Hospital	Ramat Gan		Israel	5262100
34	U.O.C. Ematologia Oncoematologia Pediatrica	Pavia	PV	Italy	27100
35	Fondazione MBBM-Clinica Pediatrica	Monza		Italy	20900
36	Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica	Roma		Italy	00165
37	S.C. Farmacia Pediatrica - Presidio Ospedaliero Infantile Regina Margherita	Turin		Italy	10126
38	Seoul National University Hospital	Seoul		Korea, Republic of	03080
39	Asan Medical Center	Seoul		Korea, Republic of	05505
40	Samsung Medical Center	Seoul		Korea, Republic of	06351
41	Seoul Saint Mary's Hospital	Seoul		Korea, Republic of	06591
42	Princess Maxima Center	Utrecht		Netherlands	3584 CS
43	Federal State Budgetary Institution "Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology	Moscow		Russian Federation	117997
44	Federal State Budgetary Educational Institution of Higher Professional Education "LP.Pavlov First Saint Petersburg State Medical	Saint Petersburg		Russian Federation	197022
45	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
46	Hospital Infantil Universitario Nino Jesus	Madrid		Spain	28009
47	Hospital Universitario Universitario La Paz	Madrid		Spain	28046
48	Safari Day Care, Great Ormond Street Hospital	London	Greater London	United Kingdom	WC1N 3JH