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

Primary Purpose

Chronic Graft Versus Host Disease

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ibrutinib
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Key Eligibility:

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)

Sites / Locations

  • City of Hope
  • Rady Children's Hospital
  • University of California
  • Children's Hospital
  • Children's National Medical Center
  • Johns Hopkins All Children's Hospital
  • Ann & Robert H Lurie Children's Hospital of Chicago
  • Johns Hopkins University
  • Dana-Farber Cancer Institute
  • University of Minnesota Masonic Children's Hospital
  • Washington University
  • Hackensack University Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Cincinnati Children's Hospital Medical Center
  • Oregon Health and Science University
  • The Children's Hospital of Philadelphia
  • St. Jude Children's Research Hospital
  • Primary Children's Hospital
  • Fred Hutchinson Cancer Research Center
  • Medical College of Wisconsin
  • Cancer Center for Children. The Children's Hospital at Westmead
  • Queensland Children's Hospital
  • The Royal Children's Hospital
  • Sydney Children's Hospital
  • St. Anna Kinderspital
  • children's and Women's Health Centre of British Columbia
  • CHU Sainte-Justine
  • CHU Nantes - Hopital Enfant Adolescent
  • Hôpital Robert-Debré Ap-Hp
  • Charite-Universitaetsmedizin Berlin
  • Hadassah Medical Centre
  • Schneider Children's Medical Center in Israel
  • The Edmond and Lily Safra Children's Hospital
  • U.O.C. Ematologia Oncoematologia Pediatrica
  • Fondazione MBBM-Clinica Pediatrica
  • Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
  • S.C. Farmacia Pediatrica - Presidio Ospedaliero Infantile Regina Margherita
  • Seoul National University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Seoul Saint Mary's Hospital
  • Princess Maxima Center
  • Federal State Budgetary Institution "Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
  • Federal State Budgetary Educational Institution of Higher Professional Education "LP.Pavlov First Saint Petersburg State Medical
  • Hospital Universitario Vall d'Hebron
  • Hospital Infantil Universitario Nino Jesus
  • Hospital Universitario Universitario La Paz
  • Safari Day Care, Great Ormond Street Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Phase 1/2

Arm Description

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.

Outcomes

Primary Outcome Measures

Part A- PK (measured by AUC) will be reported descriptively
Part B- PK (measured by AUC) will be reported descriptively
Number of patients with adverse events as a measure of safety and tolerability

Secondary Outcome Measures

Part A- Number of patients with adverse events as a measure of safety and tolerability
Part A- Pharmacodynamic effects as measured by in vitro BTK occupancy will be reported descriptively
Part A continuation cohort and Part B-Response rate at 24 weeks
Part A continuation cohort and Part B- Duration of response (DOR)
Part A continuation cohort and Part B-Overall survival (OS)
Part A continuation cohort and Part B-Late Effects Surveillance
Growth Parameter height in meters will be reported descriptively
Subjects will be monitored for growth and development
Growth Parameter weight in kilograms will be reported descriptively.
Subjects will be monitored for growth and development
Available immune reconstitution laboratory parameters will be reported descriptively
Subjects will be monitored for immune reconstitution
Late effects (Adverse events suspected to be related to treatment) will be quantified and reported descriptively

Full Information

First Posted
December 12, 2018
Last Updated
July 15, 2022
Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT03790332
Brief Title
Phase 1/2 Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects With Chronic Graft Versus Host Disease (cGVHD)
Official Title
Phase 1/2 Dose Finding and Safety Study of Ibrutinib in Pediatric Subjects With Chronic Graft Versus Host Disease (cGVHD)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 19, 2018 (Actual)
Primary Completion Date
January 4, 2026 (Anticipated)
Study Completion Date
January 4, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
Collaborators
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1/2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Other Intervention Name(s)
IMBRUVICA®, PCI-32765
Intervention Description
Ibrutinib capsule, tablet, or suspension administered orally once daily
Primary Outcome Measure Information:
Title
Part A- PK (measured by AUC) will be reported descriptively
Time Frame
Approximately 24 months
Title
Part B- PK (measured by AUC) will be reported descriptively
Time Frame
Approximately 7 years
Title
Number of patients with adverse events as a measure of safety and tolerability
Time Frame
Approximately 7 years
Secondary Outcome Measure Information:
Title
Part A- Number of patients with adverse events as a measure of safety and tolerability
Time Frame
Approximately 24 months
Title
Part A- Pharmacodynamic effects as measured by in vitro BTK occupancy will be reported descriptively
Time Frame
Approximately 24 months
Title
Part A continuation cohort and Part B-Response rate at 24 weeks
Time Frame
Approximately 6 months after last subject in enrolled
Title
Part A continuation cohort and Part B- Duration of response (DOR)
Time Frame
Up to 48 weeks
Title
Part A continuation cohort and Part B-Overall survival (OS)
Time Frame
Approximately 5 years after last subject enrolled
Title
Part A continuation cohort and Part B-Late Effects Surveillance
Time Frame
Up to 5 years post enrollment
Title
Growth Parameter height in meters will be reported descriptively
Description
Subjects will be monitored for growth and development
Time Frame
Up to 5 years post enrollment
Title
Growth Parameter weight in kilograms will be reported descriptively.
Description
Subjects will be monitored for growth and development
Time Frame
Up to 5 years post enrollment
Title
Available immune reconstitution laboratory parameters will be reported descriptively
Description
Subjects will be monitored for immune reconstitution
Time Frame
Up to 5 years post enrollment
Title
Late effects (Adverse events suspected to be related to treatment) will be quantified and reported descriptively
Time Frame
Up to 5 years post enrollment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gauri Sunkersett
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Rady Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of California
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Johns Hopkins All Children's Hospital
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Ann & Robert H Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota Masonic Children's Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55454
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105-2729
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Cancer Center for Children. The Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Queensland Children's Hospital
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
The Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Sydney Children's Hospital
City
Randwick
ZIP/Postal Code
2031
Country
Australia
Facility Name
St. Anna Kinderspital
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
children's and Women's Health Centre of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T1C5
Country
Canada
Facility Name
CHU Nantes - Hopital Enfant Adolescent
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Robert-Debré Ap-Hp
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Charite-Universitaetsmedizin Berlin
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Hadassah Medical Centre
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Schneider Children's Medical Center in Israel
City
Petach Tikva
ZIP/Postal Code
4920235
Country
Israel
Facility Name
The Edmond and Lily Safra Children's Hospital
City
Ramat Gan
ZIP/Postal Code
5262100
Country
Israel
Facility Name
U.O.C. Ematologia Oncoematologia Pediatrica
City
Pavia
State/Province
PV
ZIP/Postal Code
27100
Country
Italy
Facility Name
Fondazione MBBM-Clinica Pediatrica
City
Monza
ZIP/Postal Code
20900
Country
Italy
Facility Name
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
S.C. Farmacia Pediatrica - Presidio Ospedaliero Infantile Regina Margherita
City
Turin
ZIP/Postal Code
10126
Country
Italy
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul Saint Mary's Hospital
City
Seoul
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Princess Maxima Center
City
Utrecht
ZIP/Postal Code
3584 CS
Country
Netherlands
Facility Name
Federal State Budgetary Institution "Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
City
Moscow
ZIP/Postal Code
117997
Country
Russian Federation
Facility Name
Federal State Budgetary Educational Institution of Higher Professional Education "LP.Pavlov First Saint Petersburg State Medical
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Infantil Universitario Nino Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hospital Universitario Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Safari Day Care, Great Ormond Street Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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