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

November 7, 2022 updated by: Janssen Research & Development, LLC

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussel, Belgium
      • Leuven, Belgium
  • Brazil
      • Barretos, Brazil
      • Curitiba, Brazil
      • Sao Paulo, Brazil
      • São Paulo, Brazil
  • Bulgaria
      • Plovdiv, Bulgaria
      • Sofia, Bulgaria
  • Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
    • Ontario
      • Toronto, Ontario, Canada
  • Czechia
      • Brno, Czechia
      • Praha, Czechia
  • France
      • Bordeaux, France
      • Lille, France
      • Lyon, France
      • Marseille, France
      • Nantes, France
      • Toulouse, France
      • Vandoeuvre les Nancy, France
      • Villejuif, France
  • Germany
      • Berlin, Germany
      • Freiburg, Germany
      • Kiel, Germany
      • München, Germany
      • Münster, Germany
  • Hungary
      • Budapest, Hungary
      • Debrecen, Hungary
  • Korea, Republic of
      • Seoul, Korea, Republic of
  • Netherlands
      • Rotterdam, Netherlands
      • Utrecht, Netherlands
  • Poland
      • Krakow, Poland
      • Warszawa, Poland
      • Wroclaw, Poland
  • Romania
      • Bucuresti, Romania
      • Cluj-Napoca, Romania
      • Oradea, Romania
      • Timisoara, Romania
  • Russian Federation
      • Ekaterinburg, Russian Federation
      • Moscow, Russian Federation
      • St. Petersburg, Russian Federation
  • Spain
      • Barcelona, Spain
      • Esplugues de Llobregat, Spain
      • Madrid, Spain
      • Valencia, Spain
  • Sweden
      • Gothenburg, Sweden
  • Taiwan
      • Kaohsiung, Taiwan
      • Taipei, Taiwan
      • Taoyuan, Taiwan
  • Turkey
      • Ankara, Turkey
      • Izmir, Turkey
  • Ukraine
      • Kiev, Ukraine
  • United Kingdom
      • Birmingham, United Kingdom
      • Cambridge, United Kingdom
      • Leeds, United Kingdom
      • Liverpool, United Kingdom
      • London, United Kingdom
      • Manchester, United Kingdom
      • Newcastle, United Kingdom
      • Sheffield, United Kingdom
      • Surrey, United Kingdom
  • United States
    • California
      • Los Angeles, California, United States
      • Orange, California, United States
      • Palo Alto, California, United States
    • Colorado
      • Aurora, Colorado, United States
    • District of Columbia
      • Washington, District of Columbia, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Massachusetts
      • Boston, Massachusetts, United States
    • New York
      • New York, New York, United States
      • Valhalla, New York, United States
    • North Carolina
      • Charlotte, North Carolina, United States
    • Ohio
      • Cincinnati, Ohio, United States
      • Columbus, Ohio, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • Dallas, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part 1: Ibrutinib
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.
Drug: Ibrutinib
Participants will receive Ibrutinib (dose 240 mg/m^2 /329 mg/m^2 per day) during part 1 and part 2.
Drug: Rituximab
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.
Drug: Ifosfamide
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.
Drug: Carboplatin
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.
Drug: Etoposide
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.
Drug: Vincristine
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.
Drug: Idarubicin
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.
Drug: Dexamethasone
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.
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 per day) during part 1 and part 2.
Drug: Rituximab
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.
Drug: Ifosfamide
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.
Drug: Carboplatin
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.
Drug: Etoposide
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.
Drug: Vincristine
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.
Drug: Idarubicin
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.
Drug: Dexamethasone
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 1: Relationship Between AUC and Body Size
Time Frame: Up to Cycle 3 (each cycle of 28 days)
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.
Up to Cycle 3 (each cycle of 28 days)
Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups
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)
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.
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 Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 1 and Part 2: Overall Response Rate (ORR)
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline
Time Frame: 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.
Baseline
Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements
Time Frame: At baseline (Cycle 1 Day 1) of Part 1 and 2
Number of participants with immunoglobulin and T-cell receptor gene rearrangements were reported.
At baseline (Cycle 1 Day 1) of Part 1 and 2
Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy
Time Frame: Up to 3 months
Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy.
Up to 3 months
Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability
Time Frame: Day 1 of Cycle 1 and Cycle 3
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.
Day 1 of Cycle 1 and Cycle 3
Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations
Time Frame: Up to 4 years and 4 months
Number of Participants with CD79B, CARD11, and MYD Mutations were reported.
Up to 4 years and 4 months
Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 1: Number of Participants With c-MYC Gene Rearrangement
Time Frame: At baseline (Cycle 1 Day 1)
Number of participants with c-MYC gene rearrangement were reported.
At baseline (Cycle 1 Day 1)
Part 2: Number of Participants With c-MYC Gene Rearrangement
Time Frame: At baseline (Cycle 1 Day 1)
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.
At baseline (Cycle 1 Day 1)
Part 2: Percentage of Participants Who Achieved Complete Response (CR)
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 2: Percentage of Participants Who Achieved Partial Response (PR)
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 2: Tumor Volume Reduction Rate at Day 14
Time Frame: 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.
At Day 14
Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation
Time Frame: Up to end of the study (Up to 4 year and 4 months)
Number of participants who proceeded to stem cell transplantation were reported.
Up to end of the study (Up to 4 year and 4 months)
Part 2: Time to Response
Time Frame: Up to 4 Years and 4 months
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.
Up to 4 Years and 4 months
Part 2: Duration of Response
Time Frame: Up to 4 year and 4 months
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.
Up to 4 year and 4 months
Part 2: Percentage of Participants With EFS at 2 Years
Time Frame: 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.
At 2 years
Part 2: Percentage of Participants With EFS at 3 Years
Time Frame: 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.
At 3 years
Part 2: Overall Survival
Time Frame: Up to 4 year and 4 months
Overall survival was defined as duration from the date of randomization to the date of the participant's death.
Up to 4 year and 4 months
Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
Time Frame: Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
Part 2: Relationship Between AUC and Body Size
Time Frame: Up to Cycle 3 (each cycle of 28 days)
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. This outcome measure was planned to be analyzed for specified arm only.
Up to Cycle 3 (each cycle of 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 11, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 11, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 3, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 2, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 7, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR108134
  • 54179060LYM3003 (Other Identifier: Janssen Research & Development, LLC)
  • 2016-000259-28 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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