NCT02703272|TerminatedPhase 3ResultsDMC

Study 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).

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

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

Janssen Research & Development, LLC ClinicalTrials.gov

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3 other identifiers

CR10813454179060LYM30032016-000259-28

Study Type

interventional

Target

Locations

20 countries

Sites

Timeline

RegisteredMar 2016

StartedJul 2016

CompletionJun 2021

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).

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

Completed

Started Jul 2016

Longer than P75 for phase_3

Geographic Reach

20 countries

76 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.9 years study duration

First Submitted

Initial submission to the registry

March 3, 2016

Completed

6 days until next milestone

First Posted

Study publicly available on registry

March 9, 2016

Completed

4 months until next milestone

Study Start

First participant enrolled

July 1, 2016

Completed

4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 11, 2021

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 11, 2021

Completed

1.5 years until next milestone

Results Posted

Study results publicly available

December 2, 2022

Completed

Last Updated

December 2, 2022

Status Verified

November 1, 2022

Enrollment Period

4.9 years

First QC Date

March 3, 2016

Results QC Date

June 10, 2022

Last Update Submit

November 7, 2022

Conditions

Lymphoma, Non-Hodgkin

Keywords

Lymphoma, Non-HodgkinIbrutinibJNJ-54179060

Outcome Measures

Primary Outcomes (6)

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.
Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 21 or 28 days)
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.
Up to Cycle 3 (each cycle of 28 days)
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.
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 Outcomes (24)

Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability
Up to 4 year and 4 months
Part 1 and Part 2: Overall Response Rate (ORR)
Up to 4 year and 4 months
Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline
Baseline
Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements
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
Up to 3 months
+19 more secondary outcomes

Study Arms (2)

Part 1: Ibrutinib

EXPERIMENTAL

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: IbrutinibDrug: RituximabDrug: IfosfamideDrug: CarboplatinDrug: EtoposideDrug: VincristineDrug: IdarubicinDrug: Dexamethasone

Part 2: Ibrutinib

EXPERIMENTAL

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: IbrutinibDrug: RituximabDrug: IfosfamideDrug: CarboplatinDrug: EtoposideDrug: VincristineDrug: IdarubicinDrug: Dexamethasone

Interventions

IbrutinibDRUG

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