Mature B-Cell Neoplasm MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Current Sponsor code: JNJ-54179060
Other descriptive name:
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participants with 1 to less 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 - ICF must be signed by legally authorized representative or by the subject if at legal age of consent indicating understanding of the purpose of, and procedures required for, the study and willingness to participate in the study. Assent is also required of children capable of understanding the nature of the study per country-specific or site-specific standards as described in Section 16.2.3, Informed Consent and Assent Form. - 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 - Adolescents/young women of childbearing potential must be practicing a highly effective method of contraception (failure rate of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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) - Participants who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within at least 3 months after the last dose of ibrutinib or 1 year after the last dose of the background CIT, whichever is later - A diagnosis of post-transplant lymphoproliferative disease (PTLD) - Patients who are within 6 months of an allogeneic bone marrow transplant -Subjects who have had prior exposure to ibrutinib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Confirm that the pharmacokinetics in pediatric subjects is consistent with that in adults Part 2: Assess efficacy (EFS) of ibrutinib in combination with RICE or RVICI background therapy compared to RICE or RVICI background therapy alone;Secondary Objective: Part 1: -Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects with B-cell malignancies -Assess anti-tumor activity of ibrutinib as add-on to RICE or RVICI regimens -Assess disease-specific biomarkers -Assess the pharmacodynamic response -Acceptability and palatability assessment of all ibrutinib formulations Part 2: -Evaluate the safety and tolerability of ibrutinib in combination with RICE or RVICI background therapy in pediatric subjects and young adults with B-cell malignancies -Determine the ORR -Evaluate tumor volume reduction at Day 14 -Determine the number and proportion of subjects who proceed to stem cell transplantation -Evaluate the time to response -Measure the duration of response -Evaluate long-term survival (EFS at 2 and 3 years) -Evaluate overall survival -Assess disease-specific biomarkers For the remaining secondary objectives, please refer to protocol page 44.;Primary end point(s): 1/ Part 1: Area Under The Plasma Concentration-Time Curve (AUC) of Ibrutinib 2/ Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib 3/ Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib 4/ Part 1: Maximum Observed Plasma Concentration (Cmax) 5/ Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size 6/ Part 2: Event-free Survival [EFS]) of Ibrutinib;Timepoint(s) of evaluation of this end point: 1-4 /Predose and at 1, 2, 4, and 6 hours postdose on Day 1 and on Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3. 5/ up to three 28-day cycles 6/ Randomization to death, disease progression, or lack of CR or PR after 3 cycles | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Part 1: Number of Participants with Adverse Events 2/ Part 1: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) 3/ Part 1: Disease-specific Biomarkers Assessment 4/ Part 1: Bruton’s tyrosine kinase (BTK) Percent Occupancy 5/ Part 1: Visual analog Scale Score for Palatability 6/ Part 2: Number of Participants with Adverse Events 7/ Part 2: Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) 8/ Part 2: Tumor Volume Reduction 9/ Part 2: Percentage of Participants who Proceed to Stem Cell Transplantation 10/ Part 2: Time to Response 11/ Part 2: Duration of Response 12/ Part 2: Percentage of Participants with Long-term Survival 13/ Part 2: Overall Survival 14/ Part 2: Disease-specific Biomarkers Assessment 15/ Part 2: Bruton’s tyrosine kinase (BTK) Percent Occupancy 16/ Part 2: Visual analog Scale Score for Palatability 17/ Part 2: Area under the plasma concentration-time curve (AUC);Timepoint(s) of evaluation of this end point: 1/Throughout the study 2&7/Treatment Phase:D14 (Cy1),end of Cy2,EOT visit;Post treatment phase: 6,12,24,36 mth post C1D1/clinical cutoff for primary endpoint/or up to 3yrs after the date of C1D1, whichever occurs first 3/Predose on C1D1, C1D7 or 8, C1D14, C2D1 or C3D1 & EOT visit 4/Predose &4hrs postdose on D1 & D7 or 8 of C1, predose on C2D1 or C3D1 & at PD or EOT visit 5/Cy1D1& Cy3D1 6/Throughout the study 8/D14 9/Cy2 (D28) 10-11/Up to 4.2yrs 12/2, 3yrs 13/Randomization to till death 14/Predose on Cy1 D1, Cy1 D7 or 8, Cy1 D14, Cy2 D1 or Cy3 D1 & EOT visit 15/Predose and 4hrs postdose on C1D1 and Predose and 4hrs postdose on C1D14 or Cy2 D1, Predose on Cy3 D1, & at PD or EOT visit 16/Cy1 D1 & Cy3 D1 17/Predose, 1, 2, 4 hrs postdose, either on D14 of Cy1 or on D1 of Cy2 | — |
Countries
Belgium, Brazil, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed