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

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.

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 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