Clinical trial · Interventional
A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
NCT02703272CI-TRIAL-00062460terminatedPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Why stopped (as posted): IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).
Summary
Brief summary (as posted)
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).
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Lymphoma, Non-Hodgkin | Non-Hodgkin Lymphoma | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Carboplatin | Drug | Carboplatin | ALIAS |
| Dexamethasone | Drug | Dexamethasone | ALIAS |
| Etoposide | Drug | Etoposide | ALIAS |
| Ibrutinib | Drug | Ibrutinib | ALIAS |
| Idarubicin | Drug | Idarubicin | ALIAS |
| Ifosfamide | Drug | Ifosfamide | ALIAS |
| Rituximab | Drug | Rituximab | ALIAS |
| Vincristine | Drug | Vincristine | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Part 1: Ibrutinib
- description
- 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.
- interventionNames
- Drug: Ibrutinib
- Drug: Rituximab
- Drug: Ifosfamide
- Drug: Carboplatin
- Drug: Etoposide
- Drug: Vincristine
- Drug: Idarubicin
- Drug: Dexamethasone
- type
- EXPERIMENTAL
- label
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 1 Year
- Maximum age
- 30 Years
Show eligibility criteria text
Inclusion Criteria: * Participants with 1 to less than (\<) 18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL) occurred at \<18 years of age (Part 2 only) * Participants must be in first recurrence and have received only one prior line of therapy or have disease that is primarily refractory to conventional therapy * Participants must have at least 1 of the following: 1 site of measurable disease greater than (\>) 1 centimeter (cm) in the longest diameter and \>1 cm in the shortest diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with blasts present * Participants with lansky-Karnofsky score of greater than or equal to (\>=) 50 * Adolescent women/young women of childbearing potential must have a negative highly sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening before enrollment/randomization. Adolescent/young women who are pregnant or breastfeeding are ineligible for this study Exclusion Criteria: * Participants with ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (example phenprocoumon), or ongoing treatment with agents known to be strong CYP3A4/5 inhibitors, or has taken any disallowed therapies as noted in Section 8.2, Prohibited Medications, before the planned first dose of study drug * Participants with inherited or acquired bleeding disorders * Participants with clinically significant arrhythmias, complex congenital heart disease, or left ventricular ejection fraction (LVEF) \<50 percent (%) or shortening fraction (SF) \<=28% * Participants with known history of human immunodeficiency virus (HIV) or active Hepatitis B or C virus * Participants with any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel * Participants with known allergies, hypersensitivity, or intolerance to ibrutinib or its excipients (refer to Investigator's Brochure) * A diagnosis of post-transplant lymphoproliferative disease (PTLD) * Participants who are within 6 months of an allogeneic bone marrow transplant * Participants who have had prior exposure to ibrutinib
References
Publications (2)
- DERIVEDBurke 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. PMID 36541957
- DERIVEDChu 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. PMID 30546948