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A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma

Primary Purpose

Lymphoma, Non-Hodgkin

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ibrutinib

Rituximab

Ifosfamide

Carboplatin

Etoposide

Vincristine

Idarubicin

Dexamethasone

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Lymphoma, Non-Hodgkin, Ibrutinib, JNJ-54179060

Eligibility Criteria

1 Year - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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 recurrence and have received only one prior line of therapy 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 and >1 cm in the shortest 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)
A diagnosis of post-transplant lymphoproliferative disease (PTLD)
Participants who are within 6 months of an allogeneic bone marrow transplant
Participants who have had prior exposure to ibrutinib

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1: Ibrutinib

Part 2: Ibrutinib

Arm Description

The first 2 participants enrolled in each age group (1-5 years, 6-11 years and 12-17 years) will receive starting dose of Ibrutinib 240 milligram per square meter (mg/m^2) for the first cycle, followed by dose escalation at the start of Cycle 2 as long as all pharmacokinetic assessments are within the expected range and there are no safety concerns. For participants being treated at 240 mg/m^2 dose level during the first cycle, the maximum dose should not exceed a total of 420 mg/day. All participants will 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 until initiating antilymphoma therapy or a conditioning regimen for stem cell transplantation during post-treatment phase.

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.

Outcomes

Primary Outcome Measures

Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 milligrams per meter square [mg/m^2], 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 1: Relationship Between AUC and Body Size

The relationship between ibrutinib metrics of systemic exposure (AUC) with body size was assessed to determine the impact on AUC which were presented per dose groups (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age groups (1-5, 6-11, 12-17 and >18 years). The data could not be analyzed in tabular format for this outcome measure as they correspond to a flat regression line in nonlinear mixed effects modeling.

Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups

EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the Independent Review Committee (IRC). CR was defined as computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions, resected residual mass that was pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50 percent (%) decrease in sum of the products of the lesion diameters (SPD) on CT or MRI; fluorodeoxyglucose (FDG)-positron emission tomography (PET) may be positive, no new or progressive disease (PD); morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.

Secondary Outcome Measures

Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability

An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Part 1 and Part 2: Overall Response Rate (ORR)

ORR was defined as the percentage of participants achieving a best overall response of either complete response (CR) (including CR biopsy-negative [CRb] and unconfirmed CR [CRu]) or partial response (PR) as evaluated by International Pediatric non-Hodgkin lymphoma (NHL) response criteria. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; bone marrow (BM) and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, 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.

Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline

Tumor formalin-fixed paraffin-embedded (FFPE) samples were taken to evaluate the baseline gene expression by disease-specific biomarkers such as BCL-2L1 (BCL-xl), BIRC2 (cIAP1), Caspase 3 (CASP3), STAT3, and SYK. Transcripts per million (TPM) is a normalization method for RNA-sequencing, which means "for every 1,000,000 RNA molecules in the RNA-sequencing tumor FFPE sample, x came from this gene/transcript.

Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements

Number of participants with immunoglobulin and T-cell receptor gene rearrangements were reported.

Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy

Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy.

Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability

Palatability of ibrutinib was measured by using a VAS. The scale is a 5-point visual analog scale incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension with a score range of 1 to 5, where 1 represents best score and 5 is worst palatability.

Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations

Number of Participants with CD79B, CARD11, and MYD Mutations were reported.

Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations

Number of participants with CD79B, CARD11, and MYD mutations were reported. Blood samples were taken to evaluate the levels of biomarkers such as CD79B, CARD11, and MYD mutations.

Part 1: Number of Participants With c-MYC Gene Rearrangement

Number of participants with c-MYC gene rearrangement were reported.

Part 2: Number of Participants With c-MYC Gene Rearrangement

Number of participants with c-MYC gene rearrangement were reported. Blood samples were taken to evaluate the levels of biomarker such as c-MYC Gene rearrangement.

Part 2: Percentage of Participants Who Achieved Complete Response (CR)

Complete response rate was defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment.

Part 2: Percentage of Participants Who Achieved Partial Response (PR)

Percentage of participants who achieved PR were assessed. PR was defined as 50% decrease in SPD on computed tomography (CT) or magnetic resonance imaging (MRI); FDG-PET may be positive; no new or PD; morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.

Part 2: Tumor Volume Reduction Rate at Day 14

The tumor volume reduction rate was defined as percent decrease in the sum of the products of the lesion diameters at Day 14. It was measured as the mean change in the sum of the products of the lesion diameters (SPD) at Day 14.

Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation

Number of participants who proceeded to stem cell transplantation were reported.

Part 2: Time to Response

Time to response was defined as the time interval from the first dose of ibrutinib to the first documented response for those participants who responded. Time to response was summarized for participants who achieved either CR (including CRb and CRu) or PR. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, 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.

Part 2: Duration of Response

Duration of response was defined as the duration from date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death, whichever occurred first. PD: >25% increase in SPD of residual lesions (calculated from nadir) on CT or MRI; Deauville score 4 or 5 on FDG-PET with increase in lesional uptake from baseline; documentation of new lesions or development of new morphologic evidence of disease in BM or CSF.

Part 2: Percentage of Participants With EFS at 2 Years

EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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.

Part 2: Percentage of Participants With EFS at 3 Years

EFS is the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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.

Part 2: Overall Survival

Overall survival was defined as duration from the date of randomization to the date of the participant's death.

Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age.

Part 2: Relationship Between AUC and Body Size

Full Information

NCT ID

NCT02703272

First Posted

March 3, 2016

Last Updated

November 7, 2022

Sponsor

Janssen Research & Development, LLC

Collaborators

Pharmacyclics LLC.

1. Study Identification

Unique Protocol Identification Number

NCT02703272

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Terminated

Why Stopped

IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).

Study Start Date

July 1, 2016 (Actual)

Primary Completion Date

June 11, 2021 (Actual)

Study Completion Date

June 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

Collaborators

Pharmacyclics LLC.

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

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

Lymphoma, Non-Hodgkin

Keywords

Lymphoma, Non-Hodgkin, Ibrutinib, JNJ-54179060

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Ibrutinib

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Ibrutinib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ibrutinib

Intervention Description

Participants will receive Ibrutinib (dose 240 mg/m^2 /329 mg/m^2 per day) during part 1 and part 2.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Intervention Description

Participants will receive a cumulative dose of rituximab 750 mg/m^2 as a part of RICE/RVICI regimen in part 1 and part 2 per cycle.

Intervention Type

Drug

Intervention Name(s)

Ifosfamide

Intervention Description

Participants will receive a cumulative dose of Ifosfamide 9 g/m^2 and 10 g/m^2 as a part of RICE and RVICI regimen respectively in part 1 and part 2 per cycle.

Intervention Type

Drug

Intervention Name(s)

Carboplatin

Intervention Description

Participants will receive a cumulative dose of carboplatin 635 mg/m^2 and 800 mg/m^2 as a part of RICE and RVICI regimen respectively in part 1 and part 2 per cycle.

Intervention Type

Drug

Intervention Name(s)

Etoposide

Intervention Description

Participants will receive a cumulative dose of etoposide 300 mg/m^2 in part 1 and part 2 as a part of RICE regimen per cycle.

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Description

Participants will receive a cumulative dose of vincristine 1.6 mg/m^2 in part 1 and part 2 as a part of RVICI regimen per cycle.

Intervention Type

Drug

Intervention Name(s)

Idarubicin

Intervention Description

Participants will receive a cumulative dose of idarubicin 20 mg/m^2 in part 1 and part 2 as a part of RVICI regimen per cycle.

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Participants will receive a cumulative dose of dexamethasone 100 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen per cycle.

Primary Outcome Measure Information:

Title

Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 1: Relationship Between AUC and Body Size

Description

Time Frame

Up to Cycle 3 (each cycle of 28 days)

Title

Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups

Description

Time Frame

Time from Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (up to 4 year and 4 months)

Secondary Outcome Measure Information:

Title

Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability

Description

Time Frame

Up to 4 year and 4 months

Title

Part 1 and Part 2: Overall Response Rate (ORR)

Description

Time Frame

Up to 4 year and 4 months

Title

Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline

Description

Time Frame

Baseline

Title

Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements

Description

Number of participants with immunoglobulin and T-cell receptor gene rearrangements were reported.

Time Frame

At baseline (Cycle 1 Day 1) of Part 1 and 2

Title

Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy

Description

Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy.

Time Frame

Up to 3 months

Title

Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability

Description

Time Frame

Day 1 of Cycle 1 and Cycle 3

Title

Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations

Description

Number of Participants with CD79B, CARD11, and MYD Mutations were reported.

Time Frame

Up to 4 years and 4 months

Title

Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations

Description

Number of participants with CD79B, CARD11, and MYD mutations were reported. Blood samples were taken to evaluate the levels of biomarkers such as CD79B, CARD11, and MYD mutations.

Time Frame

Up to 4 year and 4 months

Title

Part 1: Number of Participants With c-MYC Gene Rearrangement

Description

Number of participants with c-MYC gene rearrangement were reported.

Time Frame

At baseline (Cycle 1 Day 1)

Title

Part 2: Number of Participants With c-MYC Gene Rearrangement

Description

Number of participants with c-MYC gene rearrangement were reported. Blood samples were taken to evaluate the levels of biomarker such as c-MYC Gene rearrangement.

Time Frame

At baseline (Cycle 1 Day 1)

Title

Part 2: Percentage of Participants Who Achieved Complete Response (CR)

Description

Time Frame

Up to 4 year and 4 months

Title

Part 2: Percentage of Participants Who Achieved Partial Response (PR)

Description

Time Frame

Up to 4 year and 4 months

Title

Part 2: Tumor Volume Reduction Rate at Day 14

Description

Time Frame

At Day 14

Title

Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation

Description

Number of participants who proceeded to stem cell transplantation were reported.

Time Frame

Up to end of the study (Up to 4 year and 4 months)

Title

Part 2: Time to Response

Description

Time Frame

Up to 4 Years and 4 months

Title

Part 2: Duration of Response

Description

Time Frame

Up to 4 year and 4 months

Title

Part 2: Percentage of Participants With EFS at 2 Years

Description

EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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.

Time Frame

At 2 years

Title

Part 2: Percentage of Participants With EFS at 3 Years

Description

Time Frame

At 3 years

Title

Part 2: Overall Survival

Description

Overall survival was defined as duration from the date of randomization to the date of the participant's death.

Time Frame

Up to 4 year and 4 months

Title

Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Description

Time Frame

Up to Cycle 3 (each cycle of 21 or 28 days)

Title

Part 2: Relationship Between AUC and Body Size

Description

Time Frame

Up to Cycle 3 (each cycle of 28 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility 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 recurrence and have received only one prior line of therapy 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 and >1 cm in the shortest 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) A diagnosis of post-transplant lymphoproliferative disease (PTLD) Participants who are within 6 months of an allogeneic bone marrow transplant Participants who have had prior exposure to ibrutinib

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Los Angeles

State/Province

California

Country

United States

City

Orange

State/Province

California

Country

United States

City

Palo Alto

State/Province

California

Country

United States

City

Aurora

State/Province

Colorado

Country

United States

City

Washington

State/Province

District of Columbia

Country

United States

City

Atlanta

State/Province

Georgia

Country

United States

City

Baltimore

State/Province

Maryland

Country

United States

City

Boston

State/Province

Massachusetts

Country

United States

City

New York

State/Province

New York

Country

United States

City

Valhalla

State/Province

New York

Country

United States

City

Charlotte

State/Province

North Carolina

Country

United States

City

Cincinnati

State/Province

Ohio

Country

United States

City

Columbus

State/Province

Ohio

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Dallas

State/Province

Texas

Country

United States

City

Salt Lake City

State/Province

Utah

Country

United States

City

Milwaukee

State/Province

Wisconsin

Country

United States

City

Brussel

Country

Belgium

City

Leuven

Country

Belgium

City

Barretos

Country

Brazil

City

Curitiba

Country

Brazil

City

Sao Paulo

Country

Brazil

City

São Paulo

Country

Brazil

City

Plovdiv

Country

Bulgaria

City

Sofia

Country

Bulgaria

City

Halifax

State/Province

Nova Scotia

Country

Canada

City

Toronto

State/Province

Ontario

Country

Canada

City

Brno

Country

Czechia

City

Praha

Country

Czechia

City

Bordeaux

Country

France

City

Lille

Country

France

City

Lyon

Country

France

City

Marseille

Country

France

City

Nantes

Country

France

City

Toulouse

Country

France

City

Vandoeuvre les Nancy

Country

France

City

Villejuif

Country

France

City

Berlin

Country

Germany

City

Freiburg

Country

Germany

City

Kiel

Country

Germany

City

München

Country

Germany

City

Münster

Country

Germany

City

Budapest

Country

Hungary

City

Debrecen

Country

Hungary

City

Seoul

Country

Korea, Republic of

City

Rotterdam

Country

Netherlands

City

Utrecht

Country

Netherlands

City

Krakow

Country

Poland

City

Warszawa

Country

Poland

City

Wroclaw

Country

Poland

City

Bucuresti

Country

Romania

City

Cluj-Napoca

Country

Romania

City

Oradea

Country

Romania

City

Timisoara

Country

Romania

City

Ekaterinburg

Country

Russian Federation

City

Moscow

Country

Russian Federation

City

St. Petersburg

Country

Russian Federation

City

Barcelona

Country

Spain

City

Esplugues de Llobregat

Country

Spain

City

Madrid

Country

Spain

City

Valencia

Country

Spain

City

Gothenburg

Country

Sweden

City

Kaohsiung

Country

Taiwan

City

Taipei

Country

Taiwan

City

Taoyuan

Country

Taiwan

City

Ankara

Country

Turkey

City

Izmir

Country

Turkey

City

Kiev

Country

Ukraine

City

Birmingham

Country

United Kingdom

City

Cambridge

Country

United Kingdom

City

Leeds

Country

United Kingdom

City

Liverpool

Country

United Kingdom

City

London

Country

United Kingdom

City

Manchester

Country

United Kingdom

City

Newcastle

Country

United Kingdom

City

Sheffield

Country

United Kingdom

City

Surrey

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

30546948

Citation

Chu Y, Lee S, Shah T, Yin C, Barth M, Miles RR, Ayello J, Morris E, Harrison L, Van de Ven C, Galardy P, Goldman SC, Lim MS, Hermiston M, McAllister-Lucas LM, Giulino-Roth L, Perkins SL, Cairo MS. Ibrutinib significantly inhibited Bruton's tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model. Oncoimmunology. 2018 Oct 11;8(1):e1512455. doi: 10.1080/2162402X.2018.1512455. eCollection 2019.

Results Reference

derived

Learn more about this trial

A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma

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