Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272).

Cancer and Blood Disease Institute Children's Hospital Los Angeles Los Angeles CA

Clinical Biostats Janssen Research and Development Raritan NJ

Clinical Oncology Janssen Research and Development High Wycombe United Kingdom

Clinical Oncology Janssen Research and Development Raritan NJ

Department of Hemato Oncology Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

Department of Oncology KU Leuven Leuven Belgium

Department of Paediatric Haematology Oncology and Palliative Care Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital Cambridge United Kingdom

Department of Pediatric and Adolescent Oncology INSERM U1015 Gustave Roussy Université Paris Saclay Villejuif France

Department of Pediatric Hematology and Oncology Ankara University Cebeci Hospital Ankara Turkey

Department of Pediatric Hematology and Oncology Charles University and University Hospital Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology University Hospitals Leuven Leuven Belgium

Department of Pediatric Hematology Oncology and Cell and Gene Therapy Ospedale Pediatrico Bambino Gesù Rome Italy

Department of Pediatric Hematology Oncology Erasmus MC Sophia Children's Hospital Rotterdam The Netherlands

Department of Pediatrics Seoul National University College of Medicine Seoul National University Cancer Research Institute Wide River Institute of Immunology Seoul National University Children's Hospital Seoul South Korea

Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Children's Hospital Medical Center Cincinnati OH

Departments of Pediatrics Medicine Pathology Microbiology and Immunology and Cell Biology New York Medical College Valhalla NY

Oncology Translational Research Janssen Research and Development Lower Gwynedd Township PA

Pediatric Hematology and Oncology University Hospital Münster Münster Germany

Pediatric Oncology Institute GRAACC São Paulo Brazil

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ClinicalTrials.gov
NCT02703272