Trial reportPharmaceutical research2019
Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic Results and Modeling Based on the HELIOS Trial.
Trial report in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01611090 (Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.
- The pharmacokinetics and its covariates of rituximab in different clinical populations: a systematic review and narrative synthesis.European journal of clinical pharmacology · 2026Pooled it
- Immunoglobulin G Receptors (FcγR), in Addition to Target-Antigen and Neonatal Fc Receptor (FcRn), Influence Rituximab Pharmacokinetics.Clinical pharmacokinetics · 2025Article
- Antibody Drug Clearance: An Underexplored Marker of Outcomes with Checkpoint Inhibitors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- The Influence of Underlying Disease on Rituximab Pharmacokinetics May be Explained by Target-Mediated Drug Disposition.Clinical pharmacokinetics · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 16 institutions in 11 countries.
Funding
Abstract
introductionIn the HELIOS trial, bendamustine/rituximab (BR) plus ibrutinib (BR-I) improved disease outcomes versus BR plus placebo in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma. Here, we describe the pharmacokinetic (PK) observations, along with modeling to further explore the interaction between ibrutinib and rituximab.
methods578 subjects were randomized to ibrutinib or placebo with BR (6 cycles). Ibrutinib PK samples and tumor measurements were obtained from all subjects; a subset was evaluated for bendamustine and rituximab PK. Population rituximab PK was assessed using nonlinear mixed-effects modeling.
resultsDose-normalized plasma concentration-time bendamustine data were comparable between the arms. Systemic rituximab exposure was higher with BR-I versus BR; mean trough serum concentrations were 2- to 3-fold higher in the first three cycles and 1.2- to 1.7-fold higher subsequently. No relevant safety differences were observed. In the modeling, including treatment arm as a categorical covariate and tumor burden as a continuous time-varying covariate on overall rituximab clearance significantly improved fitting of the data.
conclusionsBR-I led to higher dose-normalized systemic rituximab exposure versus BR and more rapid steady-state achievement. The modeling data suggest that rituximab disposition is, at least in part, target mediated. Determining the clinical significance of these findings requires further assessments.
trial registrationThis study is registered at https://clinicaltrials.gov/ct2/show/NCT01611090 .
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