Children's National

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

Purpose

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).

Condition

Lymphoma, Non-Hodgkin

Eligibility

Eligible Ages: Between 1 Year and 30 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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 Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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.

Recruiting Locations

More Details

NCT ID: NCT02703272
Status: Terminated
Sponsor: Janssen Research & Development, LLC

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.