Clinical trial NCT02703272: A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Lymphoma, Non-Hodgkin
Keywords: Lymphoma, Non-Hodgkin
Ibrutinib
JNJ-54179060
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Pharmacyclics LLC.
First posted: 2016-03-09
Enrollment: 72
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 1: Relationship Between AUC and Body Size
timeFrame: Up to Cycle 3 (each cycle of 28 days)
measure: Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups
timeFrame: 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:
measure: Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability
timeFrame: Up to 4 year and 4 months
measure: Part 1 and Part 2: Overall Response Rate (ORR)
timeFrame: Up to 4 year and 4 months
measure: Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline
timeFrame: Baseline
measure: Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements
timeFrame: At baseline (Cycle 1 Day 1) of Part 1 and 2
measure: Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy
timeFrame: Up to 3 months
measure: Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability
timeFrame: Day 1 of Cycle 1 and Cycle 3
measure: Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations
timeFrame: Up to 4 years and 4 months
measure: Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations
timeFrame: Up to 4 year and 4 months
measure: Part 1: Number of Participants With c-MYC Gene Rearrangement
timeFrame: At baseline (Cycle 1 Day 1)
measure: Part 2: Number of Participants With c-MYC Gene Rearrangement
timeFrame: At baseline (Cycle 1 Day 1)
measure: Part 2: Percentage of Participants Who Achieved Complete Response (CR)
timeFrame: Up to 4 year and 4 months
measure: Part 2: Percentage of Participants Who Achieved Partial Response (PR)
timeFrame: Up to 4 year and 4 months
measure: Part 2: Tumor Volume Reduction Rate at Day 14
timeFrame: At Day 14
measure: Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation
timeFrame: Up to end of the study (Up to 4 year and 4 months)
measure: Part 2: Time to Response
timeFrame: Up to 4 Years and 4 months
measure: Part 2: Duration of Response
timeFrame: Up to 4 year and 4 months
measure: Part 2: Percentage of Participants With EFS at 2 Years
timeFrame: At 2 years
measure: Part 2: Percentage of Participants With EFS at 3 Years
timeFrame: At 3 years
measure: Part 2: Overall Survival
timeFrame: Up to 4 year and 4 months
measure: Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
timeFrame: Up to Cycle 3 (each cycle of 21 or 28 days)
measure: Part 2: Relationship Between AUC and Body Size
timeFrame: Up to Cycle 3 (each cycle of 28 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Orange
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Atlanta
country: United States
state: Georgia
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Valhalla
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Milwaukee
country: United States
state: Wisconsin
city: Brussel
country: Belgium
city: Leuven
country: Belgium
city: Barretos
country: Brazil
city: Curitiba
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Halifax
country: Canada
state: Nova Scotia
city: Toronto
country: Canada
state: Ontario
city: Brno
country: Czechia
city: Praha
country: Czechia
city: Bordeaux
country: France
city: Lille
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Toulouse
country: France
city: Vandoeuvre les Nancy
country: France
city: Villejuif
country: France
city: Berlin
country: Germany
city: Freiburg
country: Germany
city: Kiel
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Seoul
country: Korea, Republic of
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Oradea
country: Romania
city: Timisoara
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Esplugues de Llobregat
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Gothenburg
country: Sweden
city: Kaohsiung
country: Taiwan
city: Taipei
country: Taiwan
city: Taoyuan
country: Taiwan
city: Ankara
country: Turkey
city: Izmir
country: Turkey
city: Kiev
country: Ukraine
city: Birmingham
country: United Kingdom
city: Cambridge
country: United Kingdom
city: Leeds
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Surrey
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.