NCT02703272 · OUTCOME
Part 1 and Part 2: Overall Response Rate (ORR)
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- NUMBER
- Unit
- Percentage of participants
- Interval / dispersion
- Not reported
- Time frame
- Up to 4 year and 4 months
What was measured
ORR was defined as the percentage of participants achieving a best overall response of either complete response (CR) (including CR biopsy-negative \[CRb\] and unconfirmed CR \[CRu\]) or partial response (PR) as evaluated by International Pediatric non-Hodgkin lymphoma (NHL) response criteria. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; bone marrow (BM) and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, PR=50% decrease in SPD on CT or MRI; FDG-PET may be positive (deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.
Analysis population: The ITT Population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received.
Groups in this outcome
Part 1: Ibrutinib+RICE
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.
Part 1: Ibrutinib+RVICI
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.
Part 2: Ibrutinib+CIT (RICE or RVICI)
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).
Part 2: Chemoimmunotherapy
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).
| Group | Source count |
|---|---|
| Part 1: Ibrutinib+RICE | 11 |
| Part 1: Ibrutinib+RVICI | 10 |
| Part 2: Ibrutinib+CIT (RICE or RVICI) | 35 |
| Part 2: Chemoimmunotherapy | 16 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Part 1: Ibrutinib+RICE | 81.8 | Not reported | Not reported | Not reported | Not reported |
| Part 1: Ibrutinib+RVICI | 50.0 | Not reported | Not reported | Not reported | Not reported |
| Part 2: Ibrutinib+CIT (RICE or RVICI) | 68.6 | Not reported | Not reported | Not reported | Not reported |
| Part 2: Chemoimmunotherapy | 81.3 | Not reported | Not reported | Not reported | Not reported |
Complete source fields
- classes
- categories
- measurements
- group Id
- OG000
- value
- 81.8
- group Id
- OG001
- value
- 50.0
- group Id
- OG002
- value
- 68.6
- group Id
- OG003
- value
- 81.3
- denoms
- counts
- group Id
- OG000
- value
- 11
- group Id
- OG001
- value
- 10
- group Id
- OG002
- value
- 35
- group Id
- OG003
- value
- 16
- units
- Participants
- description
- ORR was defined as the percentage of participants achieving a best overall response of either complete response (CR) (including CR biopsy-negative \[CRb\] and unconfirmed CR \[CRu\]) or partial response (PR) as evaluated by International Pediatric non-Hodgkin lymphoma (NHL) response criteria. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; bone marrow (BM) and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, PR=50% decrease in SPD on CT or MRI; FDG-PET may be positive (deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells.
- groups
- description
- 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.
- id
- OG000
- title
- Part 1: Ibrutinib+RICE
- description
- 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.
- id
- OG001
- title
- Part 1: Ibrutinib+RVICI
- description
- 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).
- id
- OG002
- title
- Part 2: Ibrutinib+CIT (RICE or RVICI)
- description
- 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).
- id
- OG003
- title
- Part 2: Chemoimmunotherapy
- param Type
- NUMBER
- population Description
- The ITT Population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received.
- reporting Status
- POSTED
- time Frame
- Up to 4 year and 4 months
- title
- Part 1 and Part 2: Overall Response Rate (ORR)
- type
- SECONDARY
- unit Of Measure
- Percentage of participants
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