NYMC Faculty Publications

Ibrutinib Plus RICE or RVICI for Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma in Children and Young Adults: SPARKLE Trial

G A. Burke, Department of Paediatric Haematology, Oncology and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, United Kingdom.
Luciana Vinti, Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Edita Kabickova, Department of Pediatric Hematology and Oncology, Charles University and University Hospital Motol, Prague, Czech Republic.
Auke Beishuizen, Department of Hemato-Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Nurdan Tacyildiz, Department of Pediatric Hematology and Oncology, Ankara University Cebeci Hospital, Ankara, Turkey.
Anne Uyttebroeck, Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium.
Hyoung Jin Kang, 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.
Flavio Luisi, Pediatric Oncology Institute, GRAACC, São Paulo, Brazil.
Véronique Minard-Colin, Department of Pediatric and Adolescent Oncology, INSERM U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Birgit Burkhardt, Pediatric Hematology and Oncology, University Hospital Münster, Münster, Germany.
Monelle Tamegnon, Clinical Oncology, Janssen Research & Development, Raritan, NJ.
Steven Sun, Clinical Biostats, Janssen Research & Development, Raritan, NJ.
Madeliene Curtis, Clinical Oncology, Janssen Research & Development, High Wycombe, United Kingdom.
Sanjay Deshpande, Clinical Oncology, Janssen Research & Development, Raritan, NJ.
Kerri Nottage, Clinical Oncology, Janssen Research & Development, Raritan, NJ.
Angela Howes, Clinical Oncology, Janssen Research & Development, High Wycombe, United Kingdom.
Srimathi Srinivasan, Oncology Translational Research, Janssen Research & Development, Lower Gwynedd Township, PA.
Deepa Bhojwani, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA.
Robin Norris, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Mitchell Cairo, Departments of Pediatrics, Medicine, Pathology, Microbiology & Immunology, and Cell Biology, New York Medical College, Valhalla, NY.

Author Type(s)

Faculty

Journal Title

Blood Advances

First Page

602

Last Page

610

Document Type

Article

Publication Date

2-28-2023

Department

Pediatrics

Abstract

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).

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