A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
Summary
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).
Timeline
- Start
- 2016-07-01
- Primary completion
- 2021-06-11
- Completion
- 2021-06-11
Outcome
Missed primary endpoint
Stopped: “IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).”
paper 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); PMID 36541957 ↗
paper No EFS benefit was seen with ibrutinib. PMID 36541957 ↗
Publications
- 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.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ibrutinib | Small molecule | 240 mg/m2 | — |
| Subject | Ibrutinib | Small molecule | 329 mg/m2 | — |
| Background | Carboplatin | Small molecule | 635 mg/m2 | — |
| Background | Carboplatin | Small molecule | 800 mg/m2 | — |
| Background | Dexamethasone | Small molecule | 100 mg/m2 | — |
| Background | Etoposide | Small molecule | 300 mg/m2 | — |
| Background | Idarubicin | Small molecule | 20 mg/m2 | — |
| Background | Ifosfamide | Small molecule | 9 g | — |
| Background | Ifosfamide | Small molecule | 10 g | — |
| Background | Rituximab | Monoclonal antibody | 750 mg/m2 | — |
| Background | Vincristine | Small molecule | 1.6 mg/m2 | — |