Schéma : 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 arms:
- 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.
- 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.
Current primary outcome:
Part 1:
- Area Under The Plasma Concentration-Time Curve (AUC) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of Cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size [ Time Frame: up to three 28-day cycles ]
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) ]
Current secondary outcomes:
Part 1:
- Number of Participants with Adverse Events [ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]
- Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) [ Time Frame: Approximately up to 4.2 years ]
- Disease-specific Biomarkers Assessment [ Time Frame: Cycle 1: Days 1, and 7 or 8, Cycle 2: Day 1, and Cycle 3: Day 1 (each cycle of 28 days) and End of treatment visit (30 days after last dose) ]
- Bruton's tyrosine kinase (BTK) Percent Occupancy [ Time Frame: Predose and 4 hours postdose on Day 1, Day 7 or 8 of Cycle 1, predose on Cycle 2 Day 1 or Cycle 3 Day 1 (each cycle of 28 days), and the End-of-Treatment visit (30 days after last dose) ]
- Visual analog Scale Score for Palatability [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle of 28 days) ]
Part 2:
- Number of Participants with Adverse Events [ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]
- Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) [ Time Frame: Approximately up to 4.2 years ]
- Tumor Volume Reduction [ Time Frame: Day 14 ]
- Percentage of Participants who Proceed to Stem Cell Transplantation [ Time Frame: Cycle 2 (Day 28) ]
- Time to Response [ Time Frame: Up to 4.2 years ]
- Duration of Response [ Time Frame: Up to 4.2 years ]
- Percentage of Participants with Long-term Survival [ Time Frame: 2, 3 years ]
- Overall Survival [ Time Frame: Randomization to the date of death (maximum up to 4.2 years) ]
- Disease-specific Biomarkers Assessment [ Time Frame: Cycle 1: Days 1 and 14, Cycle 2: Day 1, Cycle 3: Day 1 (each cycle of 28 days) and End of treatment visit (30 days after last dose) ]
- Bruton's tyrosine kinase (BTK) Percent Occupancy [ Time Frame: Predose and 4 hours postdose on Cycle 1 Day 1, predose and 4 hours post dose on Cycle 1 Day 14 or Cycle 2 Day 1, predose on Cycle 3 Day 1 (each cycle of 28 days), and End-of-Treatment visit (30 days after last dose) ]
- Visual analog Scale Score for Palatability [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle of 28 days) ]
- Area under the plasma concentration-time curve (AUC) [ Time Frame: Predose, 1, 2, and 4 hours postdose, either on Cycle 1 Day 14 or Cycle 2 Day 1 (each cycle of 28 days) ]
Phase : III
Stade : NA
Rechute, Réfractaire