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

NCT ID: NCT02703272

Last Updated: 2022-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-01
• Study Completion Date: 2021-06-11

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).

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.

Conditions

Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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.

Ifosfamide

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Etoposide

Intervention Type: DRUG

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.

Vincristine

Intervention Type: DRUG

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.

Idarubicin

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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.

Ifosfamide

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Etoposide

Intervention Type: DRUG

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.

Vincristine

Intervention Type: DRUG

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.

Idarubicin

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

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.

Interventions

Ibrutinib

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

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Los Angeles, California, United States

Orange, California, United States

Palo Alto, California, United States

Aurora, Colorado, United States

Washington D.C., District of Columbia, United States

Atlanta, Georgia, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

New York, New York, United States

Valhalla, New York, United States

Charlotte, North Carolina, United States

Cincinnati, Ohio, United States

Columbus, Ohio, United States

Philadelphia, Pennsylvania, United States

Dallas, Texas, United States

Salt Lake City, Utah, United States

Milwaukee, Wisconsin, United States

Brussels, , Belgium

Leuven, , Belgium

Barretos, , Brazil

Curitiba, , Brazil

São Paulo, , Brazil

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Halifax, Nova Scotia, Canada

Toronto, Ontario, Canada

Brno, , Czechia

Prague, , Czechia

Bordeaux, , France

Lille, , France

Lyon, , France

Marseille, , France

Nantes, , France

Toulouse, , France

Vandœuvre-lès-Nancy, , France

Villejuif, , France

Berlin, , Germany

Freiburg im Breisgau, , Germany

Kiel, , Germany

München, , Germany

Münster, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Rotterdam, , Netherlands

Utrecht, , Netherlands

Krakow, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Bucharest, , Romania

Cluj-Napoca, , Romania

Oradea, , Romania

Timișoara, , Romania

Moscow, , Russia

Saint Petersburg, , Russia

Yekaterinburg, , Russia

Seoul, , South Korea

Barcelona, , Spain

Esplugues de Llobregat, , Spain

Madrid, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Kaohsiung City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Ankara, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Kiev, , Ukraine

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

Countries

United States; Belgium; Brazil; Bulgaria; Canada; Czechia; France; Germany; Hungary; Netherlands; Poland; Romania; Russia; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Burke GAA, Vinti L, Kabickova E, Beishuizen A, Tacyildiz N, Uyttebroeck A, Kang HJ, Luisi F, Minard-Colin V, Burkhardt B, Tamegnon M, Sun S, Curtis M, Deshpande S, Nottage K, Howes A, Srinivasan S, Bhojwani D, Norris R, Cairo M. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023 Feb 28;7(4):602-610. doi: 10.1182/bloodadvances.2022008802.

Reference Type: DERIVED

PMID: 36541957 (View on PubMed)

Chu Y, Lee S, Shah T, Yin C, Barth M, Miles RR, Ayello J, Morris E, Harrison L, Van de Ven C, Galardy P, Goldman SC, Lim MS, Hermiston M, McAllister-Lucas LM, Giulino-Roth L, Perkins SL, Cairo MS. Ibrutinib significantly inhibited Bruton's tyrosine kinase (BTK) phosphorylation,in-vitro proliferation and enhanced overall survival in a preclinical Burkitt lymphoma (BL) model. Oncoimmunology. 2018 Oct 11;8(1):e1512455. doi: 10.1080/2162402X.2018.1512455. eCollection 2019.

Reference Type: DERIVED

PMID: 30546948 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54179060LYM3003

Identifier Type: OTHER

Identifier Source: secondary_id

2016-000259-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108134

Identifier Type: -

Identifier Source: org_study_id