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History of Changes for Study: NCT02703272
A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
Latest version (submitted July 2, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 3, 2016 None (earliest Version on record)
2 March 24, 2016 Study Status
3 April 14, 2016 Study Status, Contacts/Locations and Oversight
4 May 4, 2016 Study Status and Contacts/Locations
5 May 25, 2016 Contacts/Locations and Study Status
6 June 15, 2016 Study Status, Contacts/Locations and Oversight
7 July 15, 2016 Recruitment Status, Study Status, Contacts/Locations and Outcome Measures
8 August 30, 2016 Study Status and Study Identification
9 September 20, 2016 Contacts/Locations and Study Status
10 October 20, 2016 Contacts/Locations and Study Status
11 November 18, 2016 Study Status and Contacts/Locations
12 December 16, 2016 Contacts/Locations and Study Status
13 January 13, 2017 Study Status and Contacts/Locations
14 February 9, 2017 Study Status and Contacts/Locations
15 March 9, 2017 Study Status, Contacts/Locations and Oversight
16 April 7, 2017 Contacts/Locations, Oversight and Study Status
17 May 24, 2017 Outcome Measures, Study Status, Contacts/Locations, Arms and Interventions, Oversight and Eligibility
18 June 1, 2017 Study Status and Contacts/Locations
19 June 29, 2017 Contacts/Locations and Study Status
20 August 4, 2017 Outcome Measures, Study Status, Contacts/Locations, Arms and Interventions, Study Design and Oversight
21 August 24, 2017 Contacts/Locations and Study Status
22 September 21, 2017 Contacts/Locations, Study Status and Oversight
23 October 19, 2017 Contacts/Locations and Study Status
24 December 13, 2017 Contacts/Locations and Study Status
25 January 10, 2018 Contacts/Locations and Study Status
26 February 7, 2018 Contacts/Locations and Study Status
27 April 5, 2018 Contacts/Locations and Study Status
28 May 11, 2018 Contacts/Locations, Study Status, Eligibility, Outcome Measures and Sponsor/Collaborators
29 May 31, 2018 Contacts/Locations and Study Status
30 June 28, 2018 Contacts/Locations and Study Status
31 July 26, 2018 Study Status and Contacts/Locations
32 August 23, 2018 Study Status and Contacts/Locations
33 September 21, 2018 Study Status and Contacts/Locations
34 October 18, 2018 Study Status and Contacts/Locations
35 November 14, 2018 Study Status, Contacts/Locations and Study Design
36 December 12, 2018 Study Status and Contacts/Locations
37 January 9, 2019 Study Status and Contacts/Locations
38 February 7, 2019 Study Status and Contacts/Locations
39 March 7, 2019 Study Status and Contacts/Locations
40 May 2, 2019 Contacts/Locations and Study Status
41 June 27, 2019 Contacts/Locations and Study Status
42 July 25, 2019 Contacts/Locations and Study Status
43 August 22, 2019 Study Status and Contacts/Locations
44 October 17, 2019 Study Status and Contacts/Locations
45 November 14, 2019 Study Status and Contacts/Locations
46 January 14, 2020 Study Status and Eligibility
47 March 5, 2020 Contacts/Locations and Study Status
48 April 2, 2020 Contacts/Locations and Study Status
49 May 28, 2020 Study Status and Contacts/Locations
50 July 23, 2020 Study Status and Contacts/Locations
51 August 20, 2020 Recruitment Status, Contacts/Locations and Study Status
52 September 17, 2020 Contacts/Locations, Study Design and Study Status
53 October 15, 2020 Study Status and Contacts/Locations
54 November 12, 2020 Study Status
55 December 10, 2020 Study Status
56 January 8, 2021 Study Status
57 February 4, 2021 Study Status
58 March 4, 2021 Study Status
59 April 1, 2021 Study Status
60 April 29, 2021 Study Status
61 May 27, 2021 Study Status
62 July 2, 2021 Recruitment Status, Study Status
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Results Submission Events
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Study NCT02703272
Submitted Date:  March 3, 2016 (v1)

Open or close this module Study Identification
Unique Protocol ID: CR108134
Brief Title: A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
Official Title: A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
Secondary IDs: 54179060LYM3003 [Janssen Research & Development, LLC]
Open or close this module Study Status
Record Verification: February 2016
Overall Status: Not yet recruiting
Study Start: May 2016
Primary Completion: June 2021 [Anticipated]
Study Completion: March 2024 [Anticipated]
First Submitted: March 3, 2016
First Submitted that
Met QC Criteria:
March 3, 2016
First Posted: March 9, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
March 3, 2016
Last Update Posted: March 9, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Janssen Research & Development, LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The purpose of this study is to confirm that the pharmacokinetics of ibrutinib in pediatric participants is consistent with that in adults (part 1) and to assess efficacy (event-free survival [EFS]) of ibrutinib in combination with rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, and idarubicin (RVICI) background therapy compared to RICE or RVICI background therapy alone (part 2).
Detailed Description: This is a Phase 3, randomized (study medication assigned to participants by chance), open-label (identity of study drug will be known to participant and study staff), controlled study which consists of two parts: Part 1 and Part 2. The Part 1 is a pharmacokinetic run-in part, which will be conducted before starting the randomized part (Part 2) of the study and Part 2 is a randomized and open-label study. Part 1 and Part 2 of the study will be conducted in 3 phases: a Pretreatment (Screening) Phase (Up to 14 days before administration of study drug), a Treatment Phase, and a Posttreatment Phase. The Treatment Phase will extend from enrollment (in Part 1) or randomization (in Part 2) until 1 of the following: 1) completion of 3 cycles of therapy, 2) transplantation, if clinically indicated, or 3) progressive disease (PD), whichever comes first. The Posttreatment Phase will continue until death, loss to follow up, consent withdrawal, or study end, whichever occurs first. The end of study is defined as when approximately 60 event-free survival (EFS) events have occurred in Part 2 (death, disease progression, or lack of complete response [CR] or partial response [PR] after 3 cycles of treatment based on blinded independent event review), or the sponsor terminates the study, whichever comes first. Participants in Part 1 will be 1 to less than (<) 18 years old. Participants in Part 2 will be 1 to 30 years old. Participants will be primarily evaluated for pharmacokinetics in part 1 and efficacy (EFS) of ibrutinib in combination with RICE or RVICI background therapy compared to RICE or RVICI background therapy alone in part 2. Participants' safety will be monitored throughout the study.
Open or close this module Conditions
Conditions: Lymphoma, Non-Hodgkin
Keywords: Lymphoma, Non-Hodgkin
Ibrutinib
JNJ-54179060
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 84 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part 1: Ibrutinib
The first 2 participants enrolled in each age group (1-5 years, 6-11 years, and 12-17 years) will be treated at a lower starting dose of Ibrutinib 240 milligram per square meter (mg/m2) for the first cycle, followed by dose escalation to 329 mg/m2 at the start of Cycle 2 as long as all pharmacokinetic assessments are within the expected range and there are no safety concerns. All participants will also receive rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone (RICE) or ituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) background therapy (investigator's choice), during treatment phase. Participants with PR or better only will receive Ibrutinib for 3 cycles, or until PD, unacceptable toxicity, or up until initiating antilymphoma therapy or a conditioning regimen for stem cell transplantation during post-treatment phase.
Drug: Ibrutinib
Participants will receive Ibrutinib (dose 240 mg/m^2 /329 mg/m^2) during part 1 and part 2.
Drug: Rituximab
Participants will receive rituximab 750 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen.
Drug: Ifosfamide
Participants will receive Ifosfamide 9 g/m^2 as a part of RICE regimen in part 1 and part 2. Participants will receive Ifosfamide10 g/m^2 as a part of RVICI regimen in part 1 and part 2.
Drug: Carboplatin
Participants will receive carboplatin 635 mg/m^2 as a part of RICE regimen in part 1 and part 2. Participants will receive carboplatin 800 mg/m^2 as a part of RVICI regimen in part 1 and part 2.
Drug: Etoposide
Participants will receive etoposide 300 mg/m^2 in part 1 and part 2 as a part of RICE regimen.
Drug: Vincristine
Participants will receive vincristine 1.6 mg/m^2 in part 1 and part 2 as a part of RVICI regimen.
Drug: Idarubicin
Participants will receive idarubicin 20 mg/m^2 in part 1 and part 2 as a part of RVICI regimen.
Drug: Dexamethasone
Participants will receive dexamethasone 100 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen.
Experimental: Part 2: Ibrutinib
Participants will either receive ibrutinib and RICE/RVICI background therapy or RICE/RVICI background therapy alone, until 3 cycles are completed or until PD or unacceptable toxicity during the treatment phase. Participants who received ibrutinib and RICE/RVICI background therapy and with PR or better only will receive ibrutinib alone for 3 cycles during post-treatment phase.
Drug: Ibrutinib
Participants will receive Ibrutinib (dose 240 mg/m^2 /329 mg/m^2) during part 1 and part 2.
Drug: Rituximab
Participants will receive rituximab 750 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen.
Drug: Ifosfamide
Participants will receive Ifosfamide 9 g/m^2 as a part of RICE regimen in part 1 and part 2. Participants will receive Ifosfamide10 g/m^2 as a part of RVICI regimen in part 1 and part 2.
Drug: Carboplatin
Participants will receive carboplatin 635 mg/m^2 as a part of RICE regimen in part 1 and part 2. Participants will receive carboplatin 800 mg/m^2 as a part of RVICI regimen in part 1 and part 2.
Drug: Etoposide
Participants will receive etoposide 300 mg/m^2 in part 1 and part 2 as a part of RICE regimen.
Drug: Vincristine
Participants will receive vincristine 1.6 mg/m^2 in part 1 and part 2 as a part of RVICI regimen.
Drug: Idarubicin
Participants will receive idarubicin 20 mg/m^2 in part 1 and part 2 as a part of RVICI regimen.
Drug: Dexamethasone
Participants will receive dexamethasone 100 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Part 1: Area Under The Plasma Concentration-Time Curve (Auc) of Ibrutinib
[ Time Frame: Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 ]

AUC is the under the plasma concentration-time curve.
2. Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib
[ Time Frame: Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 ]

CL/F is the apparent (oral) Plasma Clearance.
3. Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib
[ Time Frame: Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 ]

Vd/F is the apparent (oral) Volume of Distribution.
4. Part 1: Maximum Observed Plasma Concentration (Cmax)
[ Time Frame: Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 ]

Cmax is the maximum observed plasma concentration.
5. Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size
[ Time Frame: up to three 28-day cycles ]

The impact of age or body size on the pharmacokinetic parameters will also be investigated.
6. Part 2: Event-free Survival [EFS]) of Ibrutinib
[ Time Frame: Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years) ]

EFS is the time interval from randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the Independent Review Committee (IRC).
Secondary Outcome Measures:
1. Part 1: Number of Participants with Adverse Events
[ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]

2. Part 1: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
[ Time Frame: Treatment Phase:Day 14 (Cycle 1),end of Cycle 2,End-of-Treatment visit;Post treatment phase:every 12 weeks for first 12 months,every 6 months until PD/clinical cutoff for primary endpoint/or upto 2 years after last subject enrolled,whichever occurs first ]

CR: computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions; Resected residual mass that is pathologically negative for disease; bone marrow (BM) and cerebrospinal fluid (CSF) morphologically free of disease with no new lesions by imaging examination. PR: 50 percent (%) decrease in sum of the products of the lesion diameters (SPD) on CT or MRI; FDG-PET may be positive (Deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.
3. Part 1: Disease-specific Biomarkers Assessment
[ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 and End of treatment visit ]

Blood samples will be taken to evaluate the levels of biomarkers such as Phosphor- Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), p-signal transducer, activator of transcription 3 (STAT3), Caspase-3 and B-cell receptor (BCR)/CD79B, CARD11, and MYD Mutations.
4. Part 1: Bruton's tyrosine kinase (BTK) Percent Occupancy
[ Time Frame: 4 hours postdose on Day 1 and Day 7 or 8 of Cycle 1, predose on Cycle 2 Day 1 or Cycle 3 Day 1, and the End-of-Treatment visit ]

The pharmacodynamic activity of ibrutinib in the presence of chemoimmunotherapy (CIT) (RICE or RVICI) will be assessed by determining the percentage of probe occupancy of the BTK receptor. Blood samples will be obtained for pharmacodynamic assessments (BTK occupancy).
5. Part 1: Visual analog Scale Score for Palatability
[ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 ]

Palatability will be measured using a visual analog scale. The scale is a 10-cm visual analog scale, ranges from 0 (best palatability) to 10 (worse palatibility), incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension.
6. Part 2: Number of Participants with Adverse Events
[ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]

7. Part 2: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR)
[ Time Frame: Treatment Phase:Day 14 (Cycle 1),end of Cycle 2,End-of-Treatment visit;Post treatment phase:every 12 weeks for first 12 months,every 6 months until PD/clinical cutoff for primary endpoint/or upto 2 years after last subject enrolled,whichever occurs ]

CR: CT or MRI reveals no residual disease or new lesions; Resected residual mass that is pathologically negative for disease; BM and CSF morphologically free of disease with no new lesions by imaging examination. PR: 50% decrease in SPD on CT or MRI; FDG-PET may be positive (Deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.
8. Part 2: Tumor Volume Reduction
[ Time Frame: Day 14 ]

Tumor volume reduction will be measured by decrease in the sum of the products of the lesion diameters.
9. Part 2: Percentage of Participants who Proceed to Stem Cell Transplantation
[ Time Frame: Cycle 2 (Day 28) ]

Percentage of participants who proceeded to stem cell transplantation will be calculated.
10. Part 2: Time to Response
[ Time Frame: Up to 4.2 years ]

The time interval from the first dose of ibrutinib to the first documented response for those participants who respond.
11. Part 2: Duration of Response
[ Time Frame: up to 4.2 years ]

Duration calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of PD or death.
12. Part 2: Percentage of Participants with Long-term Survival
[ Time Frame: 2, 3 years ]

Participants with event-free survival (EFS) at 2 and 3 years will be assessed.
13. Part 2: Overall Survival
[ Time Frame: Randomization to the date of death (maximum up to 4.2 years) ]

Duration from the date of randomization to the date of the subject's death.
14. Part 2: Disease-specific Biomarkers Assessment
[ Time Frame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1 and End of treatment visit ]

Blood samples will be taken to evaluate the levels of biomarkers such as Phosphor- Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), p-signal transducer, activator of transcription 3 (STAT3), Caspase-3 and B-cell receptor (BCR)/CD79B, CARD11, and MYD Mutations.
15. Part 2: Bruton's tyrosine kinase (BTK) Percent Occupancy
[ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 ]

The pharmacodynamic activity of ibrutinib will be assessed by determining the percentage of probe occupancy of the BTK receptor. Blood samples will be obtained for pharmacodynamic assessments (BTK occupancy).
16. Part 2: Visual analog Scale Score for Palatability
[ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 ]

Palatability will be measured using a visual analog scale. The scale is a 10-cm visual analog scale, ranges from 0 (best palatability) to 10 (worse palatibility), incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension.
17. Part 2: Area under the plasma concentration-time curve (AUC)
[ Time Frame: Predose; 1, 2, and 4 hours postdose, either on Day 7 or 8 of Cycle 1 or on Day 1 of Cycle 2 (or Cycle 3) ]

AUC is the aea under the plasma concentration-time curve.
Open or close this module Eligibility
Minimum Age: 1 Year
Maximum Age: 30 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Participants with 1 to less than (<) 18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL) occurred at <18 years of age (Part 2 only)
  • Participants must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
  • Participants must have at least 1 of the following: 1 site of measurable disease greater than (>) 1 centimeter (cm) in the longest diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with blasts present
  • Participants with lansky-Karnofsky score of greater than or equal to (>=) 50
  • Adolescent women/young women of childbearing potential must have a negative highly sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening before enrollment/randomization. Adolescent/young women who are pregnant or breastfeeding are ineligible for this study

Exclusion Criteria:

- Participants with ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (example phenprocoumon), or ongoing treatment with agents known to be strong CYP3A4/5 inhibitors, or has taken any disallowed therapies as noted in Section 8.2, Prohibited Medications, before the planned first dose of study drug

  • Participants with inherited or acquired bleeding disorders
  • Participants with clinically significant arrhythmias, complex congenital heart disease, or left ventricular ejection fraction (LVEF) <50 percent (%) or shortening fraction (SF) <=28%
  • Participants with known history of human immunodeficiency virus (HIV) or active Hepatitis B or C virus
  • Participants with any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
  • Participants with known allergies, hypersensitivity, or intolerance to ibrutinib or its excipients (refer to Investigator's Brochure)
Open or close this module Contacts/Locations
Central Contact Person: This study is not yet recruiting patients. Please check back for future recruiting sites, or email
Email: JNJ.CT@sylogent.com
Study Officials: Janssen Research & Development, LLC Clinical Trial
Study Director
Janssen Research & Development, LLC
Locations: Belgium
Brussel, Belgium
Leuven, Belgium
Netherlands
Rotterdam, Netherlands
Utrecht, Netherlands
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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