A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
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ClinicalTrials.gov Identifier: NCT02703272 |
Recruitment Status :
Terminated
(IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).)
First Posted : March 9, 2016
Results First Posted : December 2, 2022
Last Update Posted : December 2, 2022
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Sponsor:
Janssen Research & Development, LLC
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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Study Type | Interventional |
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Study Design | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Lymphoma, Non-Hodgkin |
Interventions |
Drug: Ibrutinib Drug: Rituximab Drug: Ifosfamide Drug: Carboplatin Drug: Etoposide Drug: Vincristine Drug: Idarubicin Drug: Dexamethasone |
Enrollment | 72 |
Participant Flow
Recruitment Details | |
Pre-assignment Details |
Arm/Group Title | Part 1: Ibrutinib+RICE | Part 1: Ibrutinib+RVICI | Part 2: Ibrutinib+CIT (RICE or RVICI) | Part 2: Chemoimmunotherapy |
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Participants received ibrutinib based on age group and body surface area (BSA) in combination with chemoimmunotherapy (CIT) (investigator choice of RICE [rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone]). For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. Ibrutinib suspension or capsule was administered once daily starting Day 1 Cycle 1. The first 2 participants enrolled in each age group (1-5 years, 6-11 years, and 12-17 years) received Ibrutinib at a lower starting dose of 240 milligram per meter square (mg/m^2) (not to exceed 420 mg per day) for the first cycle (older children [6-17 years] were enrolled first before enrolling younger children [1-5 years]), followed by dose escalation to 329 mg/m^2 (not to exceed 560 mg per day) at the start of Cycle 2 based on the safety assessments. The RICE regimen was composed of rituximab 750 mg/m^2, ifosfamide 9 grams per meter square (g/m^2), carboplatin 635 mg/m^2, etoposide 300 mg/m^2, and dexamethasone 100 mg/m^2. Study treatment continued for 3 cycles (each cycle of 28 or 21 days), unless the participants experienced unacceptable toxicity or disease progression. | Participants received ibrutinib based on age group and BSA in combination with CIT (investigator choice of RVICI [rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone]). dexamethasone]). For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. The first 2 participants enrolled in each age group (1-5 years, 6-11 years, and 12-17 years) received Ibrutinib at a lower starting dose of 240 mg/m2 (not to exceed 420 mg per day) for the first cycle (older children [6-17 years] were enrolled first before enrolling younger children [1-5 years]), followed by dose escalation to 329 mg/m2 (not to exceed 560 mg per day) at the start of Cycle 2 based on the safety assessments. The RVICI regimen was composed of rituximab 750 mg/m^2, vincristine 1.6 mg/m^2, ifosfamide 10 g/m^2, carboplatin 800 mg/m^2, idarubicin 20 mg/m^2, and dexamethasone 100 mg/m^2. Study treatment continued for 3 cycles (each cycle of 28 or 21 days), unless the participants experienced unacceptable toxicity or disease progression. | Participants received ibrutinib based on age group and BSA in combination with CIT (investigator choice of RICE or RVICI) until 3 treatment cycles, transplantation if indicated, or until progressive disease (PD) or unacceptable toxicity. For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. Participants of age groups 1-5 years and 6-11 years received ibrutinib 440 mg/m^2, and age group 12-17 years received Ibrutinib 329 mg/m^2 (dose selected from Part 1). | Participants received CIT (investigator choice of RICE or RVICI) alone based on age group and BSA until 3 treatment cycles, transplantation if indicated, or until PD or unacceptable toxicity. For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for CNS prophylaxis in age-appropriate dosing. The RICE regimen was composed of rituximab 750 mg/m^2, ifosfamide 9 g/m2, carboplatin 635 mg/m^2, etoposide 300 mg/m^2, and dexamethasone 100 mg/m^2. The RVICI regimen was composed of rituximab 750 mg/m^2, vincristine 1.6 mg/m^2, idarubicin 20 mg/m^2, carboplatin 800 mg/m^2, ifosfamide 10 g/m^2, and dexamethasone 100 mg/m^2 (all doses represented as cumulative administered in 1 cycle). |
Period Title: Overall Study | ||||
Started | 11 | 10 | 35 | 16 |
Completed | 0 | 0 | 0 | 0 |
Not Completed | 11 | 10 | 35 | 16 |
Reason Not Completed | ||||
Death | 4 | 9 | 19 | 10 |
Withdrawal by Subject | 0 | 0 | 4 | 2 |
Study Terminated by Sponsor | 6 | 1 | 12 | 4 |
Other | 1 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Part 1: Ibrutinib+RICE | Part 1: Ibrutinib+RVICI | Part 2: Ibrutinib+CIT (RICE or RVICI) | Part 2: Chemoimmunotherapy | Total | |
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Participants received ibrutinib based on age group and body surface area (BSA) in combination with chemoimmunotherapy (CIT) (investigator choice of RICE [rituximab, ifosfamide, carboplatin, etoposide, and dexamethasone]). For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. Ibrutinib suspension or capsule was administered once daily starting Day 1 Cycle 1. The first 2 participants enrolled in each age group (1-5 years, 6-11 years, and 12-17 years) received Ibrutinib at a lower starting dose of 240 milligram per meter square (mg/m^2) (not to exceed 420 mg per day) for the first cycle (older children [6-17 years] were enrolled first before enrolling younger children [1-5 years]), followed by dose escalation to 329 mg/m^2 (not to exceed 560 mg per day) at the start of Cycle 2 based on the safety assessments. The RICE regimen was composed of rituximab 750 mg/m^2, ifosfamide 9 grams per meter square (g/m^2), carboplatin 635 mg/m^2, etoposide 300 mg/m^2, and dexamethasone 100 mg/m^2. Study treatment continued for 3 cycles (each cycle of 28 or 21 days), unless the participants experienced unacceptable toxicity or disease progression. | Participants received ibrutinib based on age group and BSA in combination with CIT (investigator choice of RVICI [rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone]). dexamethasone]). For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. The first 2 participants enrolled in each age group (1-5 years, 6-11 years, and 12-17 years) received Ibrutinib at a lower starting dose of 240 mg/m2 (not to exceed 420 mg per day) for the first cycle (older children [6-17 years] were enrolled first before enrolling younger children [1-5 years]), followed by dose escalation to 329 mg/m2 (not to exceed 560 mg per day) at the start of Cycle 2 based on the safety assessments. The RVICI regimen was composed of rituximab 750 mg/m^2, vincristine 1.6 mg/m^2, ifosfamide 10 g/m^2, carboplatin 800 mg/m^2, idarubicin 20 mg/m^2, and dexamethasone 100 mg/m^2. Study treatment continued for 3 cycles (each cycle of 28 or 21 days), unless the participants experienced unacceptable toxicity or disease progression. | Participants received ibrutinib based on age group and BSA in combination with CIT (investigator choice of RICE or RVICI) until 3 treatment cycles, transplantation if indicated, or until progressive disease (PD) or unacceptable toxicity. For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for central nervous system (CNS) prophylaxis in age-appropriate dosing. Participants of age groups 1-5 years and 6-11 years received ibrutinib 440 mg/m^2, and age group 12-17 years received Ibrutinib 329 mg/m^2 (dose selected from Part 1). | Participants received CIT (investigator choice of RICE or RVICI) alone based on age group and BSA until 3 treatment cycles, transplantation if indicated, or until PD or unacceptable toxicity. For both regimens, triple intrathecal therapy consisting of methotrexate, corticosteroid, and cytarabine will be administered for CNS prophylaxis in age-appropriate dosing. The RICE regimen was composed of rituximab 750 mg/m^2, ifosfamide 9 g/m2, carboplatin 635 mg/m^2, etoposide 300 mg/m^2, and dexamethasone 100 mg/m^2. The RVICI regimen was composed of rituximab 750 mg/m^2, vincristine 1.6 mg/m^2, idarubicin 20 mg/m^2, carboplatin 800 mg/m^2, ifosfamide 10 g/m^2, and dexamethasone 100 mg/m^2 (all doses represented as cumulative administered in 1 cycle). | Total of all reporting groups | |
Overall Number of Baseline Participants | 11 | 10 | 35 | 16 | 72 | |
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[Not Specified]
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
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Number Analyzed | 11 participants | 10 participants | 35 participants | 16 participants | 72 participants | |
10.5 (4.91) | 8.3 (3.43) | 13.9 (3.94) | 13.2 (4.37) | 12.4 (4.54) | ||
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 11 participants | 10 participants | 35 participants | 16 participants | 72 participants | |
Female |
3 27.3%
|
1 10.0%
|
12 34.3%
|
3 18.8%
|
19 26.4%
|
|
Male |
8 72.7%
|
9 90.0%
|
23 65.7%
|
13 81.3%
|
53 73.6%
|
|
Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
Number Analyzed | 11 participants | 10 participants | 35 participants | 16 participants | 72 participants |
American Indian or Alaska Native |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
|
Asian |
1 9.1%
|
0 0.0%
|
8 22.9%
|
6 37.5%
|
15 20.8%
|
|
Black or African American |
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 6.3%
|
1 1.4%
|
|
Native Hawaiian or Other Pacific Islander |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
|
White |
9 81.8%
|
10 100.0%
|
22 62.9%
|
8 50.0%
|
49 68.1%
|
|
More than one race |
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
|
Unknown or Not Reported |
1 9.1%
|
0 0.0%
|
3 8.6%
|
0 0.0%
|
4 5.6%
|
|
Other |
0 0.0%
|
0 0.0%
|
2 5.7%
|
1 6.3%
|
3 4.2%
|
|
Region of Enrollment
Measure Type: Count of Participants Unit of measure: Participants |
Number Analyzed | 11 participants | 10 participants | 35 participants | 16 participants | 72 participants |
BELGIUM |
0 0.0%
|
0 0.0%
|
2 5.7%
|
0 0.0%
|
2 2.8%
|
|
BRAZIL |
1 9.1%
|
0 0.0%
|
1 2.9%
|
2 12.5%
|
4 5.6%
|
|
BULGARIA |
0 0.0%
|
0 0.0%
|
2 5.7%
|
0 0.0%
|
2 2.8%
|
|
CANADA |
0 0.0%
|
0 0.0%
|
1 2.9%
|
0 0.0%
|
1 1.4%
|
|
CZECH REPUBLIC |
0 0.0%
|
2 20.0%
|
2 5.7%
|
0 0.0%
|
4 5.6%
|
|
FRANCE |
2 18.2%
|
1 10.0%
|
3 8.6%
|
1 6.3%
|
7 9.7%
|
|
GERMANY |
2 18.2%
|
1 10.0%
|
3 8.6%
|
0 0.0%
|
6 8.3%
|
|
ITALY |
2 18.2%
|
1 10.0%
|
4 11.4%
|
2 12.5%
|
9 12.5%
|
|
NETHERLANDS |
0 0.0%
|
0 0.0%
|
1 2.9%
|
1 6.3%
|
2 2.8%
|
|
POLAND |
0 0.0%
|
1 10.0%
|
0 0.0%
|
2 12.5%
|
3 4.2%
|
|
ROMANIA |
1 9.1%
|
0 0.0%
|
0 0.0%
|
0 0.0%
|
1 1.4%
|
|
RUSSIAN FEDERATION |
0 0.0%
|
0 0.0%
|
2 5.7%
|
0 0.0%
|
2 2.8%
|
|
SOUTH KOREA |
1 9.1%
|
0 0.0%
|
5 14.3%
|
4 25.0%
|
10 13.9%
|
|
SPAIN |
0 0.0%
|
0 0.0%
|
2 5.7%
|
0 0.0%
|
2 2.8%
|
|
SWEDEN |
0 0.0%
|
0 0.0%
|
1 2.9%
|
0 0.0%
|
1 1.4%
|
|
TAIWAN |
0 0.0%
|
0 0.0%
|
2 5.7%
|
1 6.3%
|
3 4.2%
|
|
TURKEY |
1 9.1%
|
4 40.0%
|
1 2.9%
|
2 12.5%
|
8 11.1%
|
|
UKRAINE |
0 0.0%
|
0 0.0%
|
1 2.9%
|
0 0.0%
|
1 1.4%
|
|
UNITED KINGDOM |
0 0.0%
|
0 0.0%
|
1 2.9%
|
1 6.3%
|
2 2.8%
|
|
UNITED STATES |
1 9.1%
|
0 0.0%
|
1 2.9%
|
0 0.0%
|
2 2.8%
|
Outcome Measures
Adverse Events
Limitations and Caveats
[Not Specified]
More Information
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will with hold such publication for up to an additional 60 days.
Results Point of Contact
Name/Title: | Clinical Scientist |
Organization: | Janssen Research & Development, LLC |
Phone: | 844-434-4210 |
EMail: | ClinicalTrialDisclosure@its.jnj.com |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Janssen Research & Development, LLC |
ClinicalTrials.gov Identifier: | NCT02703272 |
Other Study ID Numbers: |
CR108134 54179060LYM3003 ( Other Identifier: Janssen Research & Development, LLC ) 2016-000259-28 ( EudraCT Number ) |
First Submitted: | March 3, 2016 |
First Posted: | March 9, 2016 |
Results First Submitted: | June 10, 2022 |
Results First Posted: | December 2, 2022 |
Last Update Posted: | December 2, 2022 |