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| ID | Type | Description | Link |
|---|---|---|---|
| 54179060LYM3003 | Other Identifier | Janssen Research & Development, LLC | |
| 2016-000259-28 | EudraCT Number |
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IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).
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| Name | Class |
|---|---|
| Pharmacyclics LLC. | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Ibrutinib | Experimental | The first 2 participants enrolled in each age group (1-5 years, 6-11 years and 12-17 years) will receive starting dose of Ibrutinib 240 milligram per square meter (mg/m^2) for the first cycle, followed by dose escalation at the start of Cycle 2 as long as all pharmacokinetic assessments are within the expected range and there are no safety concerns. For participants being treated at 240 mg/m^2 dose level during the first cycle, the maximum dose should not exceed a total of 420 mg/day. All participants will receive rituximab, ifosfamide, carboplatin, etoposide and dexamethasone (RICE) or ituximab, vincristine, ifosfamide, carboplatin, idarubicin and dexamethasone (RVICI) background therapy (investigator's choice), during treatment phase. Participants with PR or better only will receive Ibrutinib for 3 cycles or until PD, unacceptable toxicity or until initiating antilymphoma therapy or a conditioning regimen for stem cell transplantation during post-treatment phase. |
|
| Part 2: Ibrutinib | Experimental | Participants will either receive ibrutinib and RICE/RVICI background therapy or RICE/RVICI background therapy alone, until 3 cycles are completed or until PD or unacceptable toxicity during the treatment phase. Participants who received ibrutinib and RICE/RVICI background therapy and with PR or better only will receive ibrutinib alone for 3 cycles during post-treatment phase. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibrutinib | Drug | Participants will receive Ibrutinib (dose 240 mg/m^2 /329 mg/m^2 per day) during part 1 and part 2. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib | AUC is defined as area under the plasma concentration-time curve. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 milligrams per meter square [mg/m^2], 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib | CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib | Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Up to 4 year and 4 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Los Angeles | California | United States | ||||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36541957 | Derived | Burke GAA, Vinti L, Kabickova E, Beishuizen A, Tacyildiz N, Uyttebroeck A, Kang HJ, Luisi F, Minard-Colin V, Burkhardt B, Tamegnon M, Sun S, Curtis M, Deshpande S, Nottage K, Howes A, Srinivasan S, Bhojwani D, Norris R, Cairo M. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023 Feb 28;7(4):602-610. doi: 10.1182/bloodadvances.2022008802. | |
| 30546948 |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 15, 2020 | Jun 10, 2022 |
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| Rituximab | Drug | Participants will receive a cumulative dose of rituximab 750 mg/m^2 as a part of RICE/RVICI regimen in part 1 and part 2 per cycle. |
|
| Ifosfamide | Drug | Participants will receive a cumulative dose of Ifosfamide 9 g/m^2 and 10 g/m^2 as a part of RICE and RVICI regimen respectively in part 1 and part 2 per cycle. |
|
| Carboplatin | Drug | Participants will receive a cumulative dose of carboplatin 635 mg/m^2 and 800 mg/m^2 as a part of RICE and RVICI regimen respectively in part 1 and part 2 per cycle. |
|
| Etoposide | Drug | Participants will receive a cumulative dose of etoposide 300 mg/m^2 in part 1 and part 2 as a part of RICE regimen per cycle. |
|
| Vincristine | Drug | Participants will receive a cumulative dose of vincristine 1.6 mg/m^2 in part 1 and part 2 as a part of RVICI regimen per cycle. |
|
| Idarubicin | Drug | Participants will receive a cumulative dose of idarubicin 20 mg/m^2 in part 1 and part 2 as a part of RVICI regimen per cycle. |
|
| Dexamethasone | Drug | Participants will receive a cumulative dose of dexamethasone 100 mg/m^2 in part 1 and part 2 as a part of RICE/RVICI regimen per cycle. |
|
| Part 1: Relationship Between AUC and Body Size | The relationship between ibrutinib metrics of systemic exposure (AUC) with body size was assessed to determine the impact on AUC which were presented per dose groups (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age groups (1-5, 6-11, 12-17 and >18 years). The data could not be analyzed in tabular format for this outcome measure as they correspond to a flat regression line in nonlinear mixed effects modeling. | Up to Cycle 3 (each cycle of 28 days) |
| Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups | EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the Independent Review Committee (IRC). CR was defined as computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions, resected residual mass that was pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50 percent (%) decrease in sum of the products of the lesion diameters (SPD) on CT or MRI; fluorodeoxyglucose (FDG)-positron emission tomography (PET) may be positive, no new or progressive disease (PD); morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. | 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) |
| Part 1 and Part 2: Overall Response Rate (ORR) | 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. | Up to 4 year and 4 months |
| Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline | Tumor formalin-fixed paraffin-embedded (FFPE) samples were taken to evaluate the baseline gene expression by disease-specific biomarkers such as BCL-2L1 (BCL-xl), BIRC2 (cIAP1), Caspase 3 (CASP3), STAT3, and SYK. Transcripts per million (TPM) is a normalization method for RNA-sequencing, which means "for every 1,000,000 RNA molecules in the RNA-sequencing tumor FFPE sample, x came from this gene/transcript. | Baseline |
| Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements | Number of participants with immunoglobulin and T-cell receptor gene rearrangements were reported. | At baseline (Cycle 1 Day 1) of Part 1 and 2 |
| Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy | Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy. | Up to 3 months |
| Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability | Palatability of ibrutinib was measured by using a VAS. The scale is a 5-point visual analog scale incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension with a score range of 1 to 5, where 1 represents best score and 5 is worst palatability. | Day 1 of Cycle 1 and Cycle 3 |
| Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations | Number of Participants with CD79B, CARD11, and MYD Mutations were reported. | Up to 4 years and 4 months |
| Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations | Number of participants with CD79B, CARD11, and MYD mutations were reported. Blood samples were taken to evaluate the levels of biomarkers such as CD79B, CARD11, and MYD mutations. | Up to 4 year and 4 months |
| Part 1: Number of Participants With c-MYC Gene Rearrangement | Number of participants with c-MYC gene rearrangement were reported. | At baseline (Cycle 1 Day 1) |
| Part 2: Number of Participants With c-MYC Gene Rearrangement | Number of participants with c-MYC gene rearrangement were reported. Blood samples were taken to evaluate the levels of biomarker such as c-MYC Gene rearrangement. | At baseline (Cycle 1 Day 1) |
| Part 2: Percentage of Participants Who Achieved Complete Response (CR) | Complete response rate was defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. | Up to 4 year and 4 months |
| Part 2: Percentage of Participants Who Achieved Partial Response (PR) | Percentage of participants who achieved PR were assessed. PR was defined as 50% decrease in SPD on computed tomography (CT) or magnetic resonance imaging (MRI); FDG-PET may be positive; no new or PD; morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. | Up to 4 year and 4 months |
| Part 2: Tumor Volume Reduction Rate at Day 14 | The tumor volume reduction rate was defined as percent decrease in the sum of the products of the lesion diameters at Day 14. It was measured as the mean change in the sum of the products of the lesion diameters (SPD) at Day 14. | At Day 14 |
| Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation | Number of participants who proceeded to stem cell transplantation were reported. | Up to end of the study (Up to 4 year and 4 months) |
| Part 2: Time to Response | Time to response was defined as the time interval from the first dose of ibrutinib to the first documented response for those participants who responded. Time to response was summarized for participants who achieved either CR (including CRb and CRu) or PR. 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; 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. | Up to 4 Years and 4 months |
| Part 2: Duration of Response | Duration of response was defined as the duration from date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death, whichever occurred first. PD: >25% increase in SPD of residual lesions (calculated from nadir) on CT or MRI; Deauville score 4 or 5 on FDG-PET with increase in lesional uptake from baseline; documentation of new lesions or development of new morphologic evidence of disease in BM or CSF. | Up to 4 year and 4 months |
| Part 2: Percentage of Participants With EFS at 2 Years | EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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. | At 2 years |
| Part 2: Percentage of Participants With EFS at 3 Years | EFS is the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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. | At 3 years |
| Part 2: Overall Survival | Overall survival was defined as duration from the date of randomization to the date of the participant's death. | Up to 4 year and 4 months |
| Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib | AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib | CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib | Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | Up to Cycle 3 (each cycle of 21 or 28 days) |
| Part 2: Relationship Between AUC and Body Size | The relationship between ibrutinib metrics of systemic exposure (AUC) with body size was assessed to determine the impact on AUC which were presented per dose groups (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age groups (1-5, 6-11, 12-17 and >18 years). The data could not be analyzed in tabular format for this outcome measure as they correspond to a flat regression line in nonlinear mixed effects modeling. This outcome measure was planned to be analyzed for specified arm only. | Up to Cycle 3 (each cycle of 28 days) |
| Orange |
| California |
| United States |
| Palo Alto | California | United States |
| Aurora | Colorado | United States |
| Washington D.C. | District of Columbia | United States |
| Atlanta | Georgia | United States |
| Baltimore | Maryland | United States |
| Boston | Massachusetts | United States |
| New York | New York | United States |
| Valhalla | New York | United States |
| Charlotte | North Carolina | United States |
| Cincinnati | Ohio | United States |
| Columbus | Ohio | United States |
| Philadelphia | Pennsylvania | United States |
| Dallas | Texas | United States |
| Salt Lake City | Utah | United States |
| Milwaukee | Wisconsin | United States |
| Brussels | Belgium |
| Leuven | Belgium |
| Barretos | Brazil |
| Curitiba | Brazil |
| São Paulo | Brazil |
| Plovdiv | Bulgaria |
| Sofia | Bulgaria |
| Halifax | Nova Scotia | Canada |
| Toronto | Ontario | Canada |
| Brno | Czechia |
| Prague | Czechia |
| Bordeaux | France |
| Lille | France |
| Lyon | France |
| Marseille | France |
| Nantes | France |
| Toulouse | France |
| Vandœuvre-lès-Nancy | France |
| Villejuif | France |
| Berlin | Germany |
| Freiburg im Breisgau | Germany |
| Kiel | Germany |
| München | Germany |
| Münster | Germany |
| Budapest | Hungary |
| Debrecen | Hungary |
| Rotterdam | Netherlands |
| Utrecht | Netherlands |
| Krakow | Poland |
| Warsaw | Poland |
| Wroclaw | Poland |
| Bucharest | Romania |
| Cluj-Napoca | Romania |
| Oradea | Romania |
| Timișoara | Romania |
| Moscow | Russia |
| Saint Petersburg | Russia |
| Yekaterinburg | Russia |
| Seoul | South Korea |
| Barcelona | Spain |
| Esplugues de Llobregat | Spain |
| Madrid | Spain |
| Valencia | Spain |
| Gothenburg | Sweden |
| Kaohsiung City | Taiwan |
| Taipei | Taiwan |
| Taoyuan | Taiwan |
| Ankara | Turkey (Türkiye) |
| Izmir | Turkey (Türkiye) |
| Kiev | Ukraine |
| Birmingham | United Kingdom |
| Cambridge | United Kingdom |
| Leeds | United Kingdom |
| Liverpool | United Kingdom |
| London | United Kingdom |
| Manchester | United Kingdom |
| Newcastle | United Kingdom |
| Sheffield | United Kingdom |
| Surrey | United Kingdom |
| Derived |
| 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. |
| FG001 | 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. |
| FG002 | 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). |
| FG003 | 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). |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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). |
| BG003 | 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). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
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| Primary | Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib | AUC is defined as area under the plasma concentration-time curve. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 milligrams per meter square [mg/m^2], 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | hours*nanogram per milliliter (h*ng/mL) | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Primary | Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib | CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | milliliter per hour (mL/h) | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Primary | Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib | Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | liter(s) | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Primary | Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | nanograms per milliliter (ng/mL) | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Primary | Part 1: Relationship Between AUC and Body Size | The relationship between ibrutinib metrics of systemic exposure (AUC) with body size was assessed to determine the impact on AUC which were presented per dose groups (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age groups (1-5, 6-11, 12-17 and >18 years). The data could not be analyzed in tabular format for this outcome measure as they correspond to a flat regression line in nonlinear mixed effects modeling. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. | Posted | Up to Cycle 3 (each cycle of 28 days) |
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| Primary | Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups | EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the Independent Review Committee (IRC). CR was defined as computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions, resected residual mass that was pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50 percent (%) decrease in sum of the products of the lesion diameters (SPD) on CT or MRI; fluorodeoxyglucose (FDG)-positron emission tomography (PET) may be positive, no new or progressive disease (PD); morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. | The intent-to-treat (ITT) population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | 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) |
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| Secondary | Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. | Safety population consisted of all participants who received at least 1 dose of treatment. | Posted | Count of Participants | Participants | Up to 4 year and 4 months |
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| Secondary | Part 1 and Part 2: Overall Response Rate (ORR) | 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. | The ITT Population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received. | Posted | Number | Percentage of participants | Up to 4 year and 4 months |
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| Secondary | Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline | Tumor formalin-fixed paraffin-embedded (FFPE) samples were taken to evaluate the baseline gene expression by disease-specific biomarkers such as BCL-2L1 (BCL-xl), BIRC2 (cIAP1), Caspase 3 (CASP3), STAT3, and SYK. Transcripts per million (TPM) is a normalization method for RNA-sequencing, which means "for every 1,000,000 RNA molecules in the RNA-sequencing tumor FFPE sample, x came from this gene/transcript. | Biomarker analyses were conducted on the ITT population. As per change in planned analysis, genetic analysis was not performed for Part 1. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Transcripts per million | Baseline |
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| Secondary | Part 1 and Part 2: Number of Participants With Immunoglobulin and T-cell Receptor Gene Rearrangements | Number of participants with immunoglobulin and T-cell receptor gene rearrangements were reported. | Biomarker analyses were conducted on the ITT population. As per change in planned analysis, immunoglobulin and T-cell receptor gene rearrangements were not performed for Part 1 and Part 2. | Posted | At baseline (Cycle 1 Day 1) of Part 1 and 2 |
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| Secondary | Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy | Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy. | Biomarker analyses were conducted on the ITT population. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. As planned, BTK occupancy was assessed for ibrutinib only. | Posted | Count of Participants | Participants | Up to 3 months |
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| Secondary | Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability | Palatability of ibrutinib was measured by using a VAS. The scale is a 5-point visual analog scale incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension with a score range of 1 to 5, where 1 represents best score and 5 is worst palatability. | Safety population: all participants who received at least 1 dose of treatment. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure (OM) and, n (number analyzed) signifies number of participants analyzed for specified category. Participants in arm 'Part 2: Chemoimmunotherapy' did not receive ibrutinib, and palatability of ibrutinib was measured in this OM. Hence, no data available to report for this arm. | Posted | Mean | Standard Deviation | Units on a scale | Day 1 of Cycle 1 and Cycle 3 |
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| Secondary | Part 1: Number of Participants With CD79B, CARD11, and MYD Mutations | Number of Participants with CD79B, CARD11, and MYD Mutations were reported. | Biomarker analyses were conducted on the ITT population. As per change in planned analysis, genetic analysis was not performed for Part 1. | Posted | Up to 4 years and 4 months |
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| Secondary | Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations | Number of participants with CD79B, CARD11, and MYD mutations were reported. Blood samples were taken to evaluate the levels of biomarkers such as CD79B, CARD11, and MYD mutations. | Biomarker analyses were conducted on the ITT population. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | Up to 4 year and 4 months |
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| Secondary | Part 1: Number of Participants With c-MYC Gene Rearrangement | Number of participants with c-MYC gene rearrangement were reported. | Biomarker analyses were conducted on the ITT population. As per change in planned analysis, genetic analysis was not performed for Part 1. | Posted | At baseline (Cycle 1 Day 1) |
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| Secondary | Part 2: Number of Participants With c-MYC Gene Rearrangement | Number of participants with c-MYC gene rearrangement were reported. Blood samples were taken to evaluate the levels of biomarker such as c-MYC Gene rearrangement. | Biomarker analyses were conducted on the ITT population. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | At baseline (Cycle 1 Day 1) |
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| Secondary | Part 2: Percentage of Participants Who Achieved Complete Response (CR) | Complete response rate was defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. | The ITT Population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received. | Posted | Number | Percentage of Participants | Up to 4 year and 4 months |
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| Secondary | Part 2: Percentage of Participants Who Achieved Partial Response (PR) | Percentage of participants who achieved PR were assessed. PR was defined as 50% decrease in SPD on computed tomography (CT) or magnetic resonance imaging (MRI); FDG-PET may be positive; no new or PD; morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. | The ITT Population consisted of all randomized participants; participants analyzed based on randomization, regardless of study drug received. | Posted | Number | percentage of participants | Up to 4 year and 4 months |
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| Secondary | Part 2: Tumor Volume Reduction Rate at Day 14 | The tumor volume reduction rate was defined as percent decrease in the sum of the products of the lesion diameters at Day 14. It was measured as the mean change in the sum of the products of the lesion diameters (SPD) at Day 14. | The ITT Population consisted of all randomized participants; participants was analyzed based on randomization, regardless of study drug received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Deviation | Percent change | At Day 14 |
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| Secondary | Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation | Number of participants who proceeded to stem cell transplantation were reported. | The ITT population consisted of all randomized participants; participants were analyzed based on randomization, regardless of study drug received. | Posted | Count of Participants | Participants | Up to end of the study (Up to 4 year and 4 months) |
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| Secondary | Part 2: Time to Response | Time to response was defined as the time interval from the first dose of ibrutinib to the first documented response for those participants who responded. Time to response was summarized for participants who achieved either CR (including CRb and CRu) or PR. 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; 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. | Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Time to response was summarized for participants who achieved either CR (including CRb and CRu) or PR. | Posted | Median | 90% Confidence Interval | Months | Up to 4 Years and 4 months |
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| Secondary | Part 2: Duration of Response | Duration of response was defined as the duration from date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death, whichever occurred first. PD: >25% increase in SPD of residual lesions (calculated from nadir) on CT or MRI; Deauville score 4 or 5 on FDG-PET with increase in lesional uptake from baseline; documentation of new lesions or development of new morphologic evidence of disease in BM or CSF. | Duration of response was summarized for participants who achieved either CR (including CRb and CRu) or PR. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. | Posted | Median | 90% Confidence Interval | Months | Up to 4 year and 4 months |
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| Secondary | Part 2: Percentage of Participants With EFS at 2 Years | EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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. | The ITT Population consisted of all randomized participants; participants were analyzed based on randomization, regardless of study drug received. | Posted | Number | Percentage of participants | At 2 years |
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| Secondary | Part 2: Percentage of Participants With EFS at 3 Years | EFS is the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, 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. | The ITT Population consisted of all randomized participants; participants were analyzed based on randomization, regardless of study drug received. | Posted | Number | Percentage of participants | At 3 years |
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| Secondary | Part 2: Overall Survival | Overall survival was defined as duration from the date of randomization to the date of the participant's death. | The ITT Population consisted of all randomized participants; participants were analyzed based on randomization, regardless of study drug received. | Posted | Median | 90% Confidence Interval | Months | Up to 4 year and 4 months |
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| Secondary | Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib | AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Mean | Full Range | h*ng/mL | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Secondary | Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib | CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | mL/h | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Secondary | Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib | Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | liter(s) | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Secondary | Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib | Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category. | Posted | Median | Full Range | ng/mL | Up to Cycle 3 (each cycle of 21 or 28 days) |
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| Secondary | Part 2: Relationship Between AUC and Body Size | The relationship between ibrutinib metrics of systemic exposure (AUC) with body size was assessed to determine the impact on AUC which were presented per dose groups (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age groups (1-5, 6-11, 12-17 and >18 years). The data could not be analyzed in tabular format for this outcome measure as they correspond to a flat regression line in nonlinear mixed effects modeling. This outcome measure was planned to be analyzed for specified arm only. | PK analysis set included participants in the ibrutinib group that received ibrutinib doses and had quantifiable plasma concentration of ibrutinib. | Posted | Up to Cycle 3 (each cycle of 28 days) |
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Up to 4 year and 4 months
The safety population consisted of all participants who received at least 1 dose of treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 4 | 11 | 10 | 11 | 11 | 11 |
| EG001 | 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. | 9 | 10 | 9 | 10 | 10 | 10 |
| EG002 | 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). | 19 | 35 | 25 | 35 | 35 | 35 |
| EG003 | 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). | 10 | 15 | 11 | 15 | 15 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Febrile Bone Marrow Aplasia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Optic Atrophy | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gastric Ulcer | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gastrointestinal Inflammation | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Lower Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Upper Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Mucosal Inflammation | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Multiple Organ Dysfunction Syndrome | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Systemic Inflammatory Response Syndrome | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hepatic Failure | Hepatobiliary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anaphylactic Reaction | Immune system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Infusion Related Hypersensitivity Reaction | Immune system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anorectal Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Capnocytophaga Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Corynebacterium Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Cryptosporidiosis Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Device Related Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Escherichia Sepsis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Klebsiella Sepsis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neutropenic Sepsis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pulmonary Mycosis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Staphylococcal Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Vascular Device Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Subdural Haematoma | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Subdural Haemorrhage | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Blood Bilirubin Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Coagulation Test Abnormal | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Platelet Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| White Blood Cell Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Altered State of Consciousness | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haemorrhage Intracranial | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hepatic Encephalopathy | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Paraplegia | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Spinal Cord Haematoma | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Subarachnoid Haemorrhage | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Tonic Convulsion | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Toxic Encephalopathy | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Psychotic Disorder | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Cystitis Haemorrhagic | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Renal Failure | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pulmonary Haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Capillary Leak Syndrome | Vascular disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 23.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Febrile Bone Marrow Aplasia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypofibrinogenaemia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Macrocytosis | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pericardial Effusion | Cardiac disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aplasia | Congenital, familial and genetic disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Ear Pain | Ear and labyrinth disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Eye Pain | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Eyelid Oedema | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Eyelid Ptosis | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Keratitis | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pupils Unequal | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Xerophthalmia | Eye disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anal Erythema | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anal Inflammation | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anal Ulcer | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anorectal Ulcer | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aphthous Ulcer | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Chapped Lips | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Dental Caries | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Enterocolitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gastrointestinal Inflammation | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gastrointestinal Motility Disorder | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gingival Bleeding | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gingival Oedema | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Intestinal Haemorrhage | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Mouth Haemorrhage | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Mouth Ulceration | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Oesophageal Pain | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rectal Haemorrhage | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Catheter Site Granuloma | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Catheter Site Pain | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Chest Pain | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Device Related Thrombosis | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Face Oedema | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Generalised Oedema | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Mucosal Inflammation | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Mucosal Ulceration | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Swelling | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Swelling Face | General disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hepatic Failure | Hepatobiliary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Drug Hypersensitivity | Immune system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anal Abscess | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aspergillus Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Bk Virus Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Device Related Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Escherichia Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fungal Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fusarium Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Geotrichum Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Klebsiella Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Oral Herpes | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pseudomonal Bacteraemia | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rhinovirus Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection Pseudomonal | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Vascular Device Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Buttock Injury | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fractured Sacrum | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Infusion Related Reaction | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Transfusion Reaction | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Traumatic Haematoma | Injury, poisoning and procedural complications | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Amylase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Antithrombin Iii Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Blood Bilirubin Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Blood Lactate Dehydrogenase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| C-Reactive Protein Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Gamma-Glutamyltransferase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haemoglobin Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| International Normalised Ratio Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Lipase Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Lymphocyte Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pancreatic Enzymes Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Platelet Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Staphylococcus Test Positive | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Weight Increased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| White Blood Cell Count Decreased | Investigations | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Fluid Retention | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Skin Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Depressed Level of Consciousness | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypersomnia | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Muscle Spasticity | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Myoclonus | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Spinal Cord Haematoma | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Toxic Encephalopathy | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Confusional State | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Post-Traumatic Stress Disorder | Psychiatric disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypotonic Urinary Bladder | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Renal Impairment | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Renal Tubular Injury | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Urinary Retention | Renal and urinary disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Penile Swelling | Reproductive system and breast disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Respiratory Alkalosis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Decubitus Ulcer | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Skin Lesion | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 23.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA Version 23.1 | Non-systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Scientist | Janssen Research & Development, LLC | 844-434-4210 | ClinicalTrialDisclosure@its.jnj.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 4, 2017 | Jun 10, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C551803 | ibrutinib |
| D000069283 | Rituximab |
| D007069 | Ifosfamide |
| D016190 | Carboplatin |
| D005047 | Etoposide |
| D014750 | Vincristine |
| D015255 | Idarubicin |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D056831 | Coordination Complexes |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D000617 | Aminoglycosides |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D013259 | Steroids, Fluorinated |
Not provided
Not provided
| Male |
|
| Asian |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Other |
|
| BRAZIL |
|
| BULGARIA |
|
| CANADA |
|
| CZECH REPUBLIC |
|
| FRANCE |
|
| GERMANY |
|
| ITALY |
|
| NETHERLANDS |
|
| POLAND |
|
| ROMANIA |
|
| RUSSIAN FEDERATION |
|
| SOUTH KOREA |
|
| SPAIN |
|
| SWEDEN |
|
| TAIWAN |
|
| TURKEY |
|
| UKRAINE |
|
| UNITED KINGDOM |
|
| UNITED STATES |
|
| 6-11 years |
|
|
| 12-17 years |
|
|
| 18+ years |
|
Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in Part 1. |
|
|
Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in part 1. |
|
|
Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in part 1. |
|
|
| OG001 | 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. |
|
| OG001 | 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). |
|
|
| OG001 | 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. |
| OG002 | 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). |
| OG003 | 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). |
|
|
| OG001 | 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. |
| OG002 | 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). |
| OG003 | 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). |
|
|
| OG001 | 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. |
| OG002 | 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). |
| OG003 | 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). |
|
|
| OG001 | 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. |
| OG002 | 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). |
| OG003 | 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). |
|
|
| OG001 | Part 2: Ibrutinib | 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. |
|
|
| OG001 | 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. |
| OG002 | 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). |
|
|
| OG001 | 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. |
|
|
|
|
| OG001 |
| 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. |
|
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| OG001 | 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). |
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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). |
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| OG001 | 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). |
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| OG001 | 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). |
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Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in part 2. |
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Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in Part 2. |
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Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in part 2. |
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Participants received 440 mg/m^2 ibrutinib based on age group for 3 treatment cycles with each cycle of 21 or 28 days long in part 2. |
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| Participants |
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