Clinical Trials List
Protocol Number54179060LYM3003
NCT Number(ClinicalTrials.gov Identfier)NCT02703272
2017-01-20 - 2022-02-17
Phase III
Terminated3
ICD-10C83.70
Burkitt lymphoma, unspecified site
ICD-10C83.79
Burkitt lymphoma, extranodal and solid organ sites
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9200.20
Burkitt's tumor or lymphoma, unspecified site, extranodal solid organ sites
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
-
Trial Applicant
Johnson & Johnson
-
Sponsor
Janssen Research & Development, LLC
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Tang-Her Jaing Division of Pediatrics
- Hung Chang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- YUNG-LI YANG Division of Others -
- 周書緯 Division of Pediatrics
- MENG-YAO LU Division of Pediatrics
- 張修豪 Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Mature B-cell Non-Hodgkin Lymphoma
Objectives
Primary
Confirm that the pharmacokinetics in pediatric
subjects is consistent with that in adults
Secondary
Evaluate the safety and tolerability of ibrutinib
in combination with rituximab, ifosfamide,
carboplatin, etoposide, and dexamethasone
(RICE) or rituximab, vincristine, ifosfamide,
carboplatin, idarubicin, and dexamethasone
(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
Test Drug
Ibrutinib
Active Ingredient
Ibrutinib
Dosage Form
Capsule
Capsule
suspension
Capsule
suspension
Dosage
140
70
70
70
70
Endpoints
Primary Outcome Measures :
Part 1: Area Under The Plasma Concentration-Time Curve (AUC) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
AUC is the under the plasma concentration-time curve.
Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of Cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
CL/F is the apparent (oral) Plasma Clearance.
Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
Vd/F is the apparent (oral) Volume of Distribution.
Part 1: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
Cmax is the maximum observed plasma concentration.
Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size [ Time Frame: up to three 28-day cycles ]
The impact of age or body size on the pharmacokinetic parameters will also be investigated.
Part 2: Event-free Survival [EFS]) of Ibrutinib [ Time Frame: Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years) ]
EFS is the time interval from randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the Independent Review Committee (IRC).
Part 1: Area Under The Plasma Concentration-Time Curve (AUC) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
AUC is the under the plasma concentration-time curve.
Part 1: Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of Cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
CL/F is the apparent (oral) Plasma Clearance.
Part 1: Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
Vd/F is the apparent (oral) Volume of Distribution.
Part 1: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
Cmax is the maximum observed plasma concentration.
Part 1: Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size [ Time Frame: up to three 28-day cycles ]
The impact of age or body size on the pharmacokinetic parameters will also be investigated.
Part 2: Event-free Survival [EFS]) of Ibrutinib [ Time Frame: Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years) ]
EFS is the time interval from randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the Independent Review Committee (IRC).
Inclution Criteria
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. 1 to <18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial
diagnosis of mature B-cell NHL occurred at <18 years of age (Part 2 only)
2. Criterion modified per amendment 1
2.1 Relapsed/refractory BL, Burkitt-like lymphoma (BLL), Burkitt leukemia
(ie, B-AL) with FAB3 morphology or presence of surface immunoglobulin by flow
cytometry, DLBCL, DLBCL not otherwise specified (NOS), or other pediatric
mature B-cell NHL
NOTE: Must have pathology report for the original NHL diagnosis. If that pathology
report is not available, the pathology results of a fresh biopsy will be required for
enrollment into the study.
3. Must be in first or later recurrence or have disease that is primarily refractory to
conventional therapy
4. Must have at least 1 of the following:
a) 1 site of measurable disease >1 cm in the longest diameter by radiological
imaging
b) bone marrow involvement
c) cerebrospinal fluid with blasts present
5. Lansky-Karnofsky score of ≥50
6. Adequate organ function defined as follows:
a) Absolute neutrophil count (ANC) 500 cells/mm3
. Growth factor support per
institutional guidelines is permitted during the Screening and Treatment
phases.
b) Platelets 50,000 cells/mm3
. Subjects with thrombocytopenia due to bone
marrow infiltration are eligible if platelets are 25,000 cells/mm3
.
Transfusion support is permitted during the Screening and Treatment phases.
c) Alanine aminotransferase 3 x upper limit of normal (ULN)
d) Aspartate aminotransferase 3 x ULN
e) Total bilirubin <1.5 x ULN, except in subjects with Gilbert syndrome or in
subjects in whom the bilirubin rise is of non-hepatic origin
f) Serum creatinine <2 x ULN for age or glomerular filtration rate
>30 mL/min/1.73 m
2
by the CKiD Schwartz equation36
7. Must have recovered from the acute toxic effects of prior chemotherapy,
immunotherapy, or radiotherapy, in the opinion of the investigator, prior to entering
this study; and hematologic toxicities must meet the above criteria
8. Criterion modified per amendment 1
8.1 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 countryspecific or site-specific standards as described in Section 16.2.3, Informed Consent
and Assent Form.
10. Criterion modified per amendment 1
10.1. Adolescents/young women of childbearing potential must be practicing a
highly effective method of contraception (failure rate of <1% per year when used
consistently and correctly) and agree to remain on a highly effective method
throughout the study and for at least 3 months after the last dose of ibrutinib and
1 year after the last dose of rituximab, whichever is later.
11. During the study and for a minimum of 1 spermatogenesis cycle (defined as
approximately 90 days) after receiving the last dose of study drug, in addition to the
user-independent highly effective method of contraception, a man
who is sexually active with a woman of childbearing potential must agree to
use a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository)
who is sexually active with a woman who is pregnant must use a condom
must agree not to donate sperm
12. Must be willing and able to adhere to the prohibitions and restrictions specified in
this protocol
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. 1 to <18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial
diagnosis of mature B-cell NHL occurred at <18 years of age (Part 2 only)
2. Criterion modified per amendment 1
2.1 Relapsed/refractory BL, Burkitt-like lymphoma (BLL), Burkitt leukemia
(ie, B-AL) with FAB3 morphology or presence of surface immunoglobulin by flow
cytometry, DLBCL, DLBCL not otherwise specified (NOS), or other pediatric
mature B-cell NHL
NOTE: Must have pathology report for the original NHL diagnosis. If that pathology
report is not available, the pathology results of a fresh biopsy will be required for
enrollment into the study.
3. Must be in first or later recurrence or have disease that is primarily refractory to
conventional therapy
4. Must have at least 1 of the following:
a) 1 site of measurable disease >1 cm in the longest diameter by radiological
imaging
b) bone marrow involvement
c) cerebrospinal fluid with blasts present
5. Lansky-Karnofsky score of ≥50
6. Adequate organ function defined as follows:
a) Absolute neutrophil count (ANC) 500 cells/mm3
. Growth factor support per
institutional guidelines is permitted during the Screening and Treatment
phases.
b) Platelets 50,000 cells/mm3
. Subjects with thrombocytopenia due to bone
marrow infiltration are eligible if platelets are 25,000 cells/mm3
.
Transfusion support is permitted during the Screening and Treatment phases.
c) Alanine aminotransferase 3 x upper limit of normal (ULN)
d) Aspartate aminotransferase 3 x ULN
e) Total bilirubin <1.5 x ULN, except in subjects with Gilbert syndrome or in
subjects in whom the bilirubin rise is of non-hepatic origin
f) Serum creatinine <2 x ULN for age or glomerular filtration rate
>30 mL/min/1.73 m
2
by the CKiD Schwartz equation36
7. Must have recovered from the acute toxic effects of prior chemotherapy,
immunotherapy, or radiotherapy, in the opinion of the investigator, prior to entering
this study; and hematologic toxicities must meet the above criteria
8. Criterion modified per amendment 1
8.1 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 countryspecific or site-specific standards as described in Section 16.2.3, Informed Consent
and Assent Form.
10. Criterion modified per amendment 1
10.1. Adolescents/young women of childbearing potential must be practicing a
highly effective method of contraception (failure rate of <1% per year when used
consistently and correctly) and agree to remain on a highly effective method
throughout the study and for at least 3 months after the last dose of ibrutinib and
1 year after the last dose of rituximab, whichever is later.
11. During the study and for a minimum of 1 spermatogenesis cycle (defined as
approximately 90 days) after receiving the last dose of study drug, in addition to the
user-independent highly effective method of contraception, a man
who is sexually active with a woman of childbearing potential must agree to
use a barrier method of contraception (eg, condom with spermicidal
foam/gel/film/cream/suppository)
who is sexually active with a woman who is pregnant must use a condom
must agree not to donate sperm
12. Must be willing and able to adhere to the prohibitions and restrictions specified in
this protocol
Exclusion Criteria
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study.
1. Ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists
(eg, 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
2. Inherited or acquired bleeding disorders
3. Clinically significant arrhythmias, complex congenital heart disease, or left ventricular
ejection fraction (LVEF) <50% or shortening fraction (SF) ≤28%
4. Known history of human immunodeficiency virus (HIV) or active Hepatitis B or C
virus
5. 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
6. Known allergies, hypersensitivity, or intolerance to ibrutinib or its excipients (refer to
Investigator's Brochure)
7. Known allergy, hypersensitivity, or intolerance to any of the backbone CIT
8. Received an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 30 days before the planned first dose of
study drug, or is currently being treated in an investigational study
9. Pregnant, or breastfeeding, or planning to become pregnant while enrolled in this
study or within 8 weeks after the last dose of study drug
10. Plans to father a child while enrolled in this study or within 3 months after the last
dose of study drug
11. Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the subject (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments
12. Had major surgery, (eg, requiring general anesthesia) within 4 weeks before
enrollment/randomization, or has not fully recovered from surgery, or has surgery
planned during the time the subject is expected to participate in the study or within
4 weeks after the last dose of study drug administration. Lumbar puncture, bone
marrow aspiration/biopsy, or placement of central venous access device are not
considered major procedures.
Any potential subject who meets any of the following criteria will be excluded from participating
in the study.
1. Ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists
(eg, 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
2. Inherited or acquired bleeding disorders
3. Clinically significant arrhythmias, complex congenital heart disease, or left ventricular
ejection fraction (LVEF) <50% or shortening fraction (SF) ≤28%
4. Known history of human immunodeficiency virus (HIV) or active Hepatitis B or C
virus
5. 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
6. Known allergies, hypersensitivity, or intolerance to ibrutinib or its excipients (refer to
Investigator's Brochure)
7. Known allergy, hypersensitivity, or intolerance to any of the backbone CIT
8. Received an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 30 days before the planned first dose of
study drug, or is currently being treated in an investigational study
9. Pregnant, or breastfeeding, or planning to become pregnant while enrolled in this
study or within 8 weeks after the last dose of study drug
10. Plans to father a child while enrolled in this study or within 3 months after the last
dose of study drug
11. Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the subject (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments
12. Had major surgery, (eg, requiring general anesthesia) within 4 weeks before
enrollment/randomization, or has not fully recovered from surgery, or has surgery
planned during the time the subject is expected to participate in the study or within
4 weeks after the last dose of study drug administration. Lumbar puncture, bone
marrow aspiration/biopsy, or placement of central venous access device are not
considered major procedures.
The Estimated Number of Participants
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Taiwan
4 participants
-
Global
93 participants
