Adaptive Platform Trial for Dose Optimization of Ibrutinib‑Based Combination Therapy in Adult Patients with Haematological Malignancies (BLOOD-dose)

The primary objective of the BLOOD‑dose platform trial is to compare overall survival between treatment intensity arms, thereby determining the optimal therapeutic dose for adult patients with haematological diseases. Secondary objectives include: - comparison of progression‑free survival between interventions; - evaluation of patient‑reported health‑related quality of life; - assessment of safety and tolerability; - analysis of the impact of treatment and disease on healthcare resource utilization; - comparison of the economic cost of the interventions.

The trial enrolled adult participants of both sexes, aged 18 years and older, who had a diagnosis of a haematological disease. The sponsor did not provide the total number of participants. Eligibility required capability to give signed informed consent and qualification for at least one of the currently active domains of the platform trial. The study population consisted of patients only; no specific dietary, physical‑activity, or other lifestyle requirements were described in the available information.

The BLOOD-dose study is a multicentre, adaptive, randomized, controlled platform trial evaluating authorized treatments in adult patients with haematological diseases to identify optimal dose intensity; recruitment is planned from January 2027 to January 2040. Eligible participants (≥18 years, diagnosed with a haematological disorder, eligible for at least one active domain, and able to give informed consent) undergo a screening visit to confirm eligibility and establish baseline core outcome measurements. After randomization, participants receive the assigned regimen (e.g., oral ibrutinib 420 mg, zanubrutinib 320 mg, subcutaneous elranatamab 76 mg, etc.) and attend follow‑up visits at predefined intervals (typically every 4 weeks) to assess safety, laboratory parameters, medication exposure, and efficacy, with the primary endpoint defined as Overall survival (OS). Secondary endpoints include progression‑free survival, health‑related quality of life, adverse event reporting, and healthcare utilisation. The end‑of‑study visit occurs after the predetermined treatment period or upon a protocol‑specified event, and participants remain in follow‑up for the full trial duration. Early termination may be triggered by unacceptable toxicity, withdrawal of consent, major protocol violations, or interim analysis results indicating futility or superiority of an arm, resulting in discontinuation of the participant’s involvement.

IBRUTINIB is administered orally in the pharmaceutical form identified as PHF00006MIG at a dose of 420 mg per administration. The product is classified as a test investigational drug and is designated as an orphan drug.

ZANUBRUTINIB is provided in the pharmaceutical form PHF00082MIG for oral use at a dose of 320 mg per administration. This investigational agent is also listed as an orphan drug.

LINVOSELTAMAB (commercially named LYNOZYFIC 5 mg concentrate for solution for infusion) is delivered by intravenous infusion. Each dose consists of 200 mg of the active substance in a solution for infusion.

ELRANATAMAB (ELREXFIO 40 mg/mL solution for injection) is given by subcutaneous injection at a dose of 76 mg per administration in a solution for injection.

TECLISTAMAB (TECVAYLI 10 mg/mL solution for injection) is administered subcutaneously at a body‑weight‑adjusted dose of 1.5 mg/kg, prepared as a solution for injection.

TALQUETAMAB (TALVEY 2 mg/mL solution for injection) is administered subcutaneously at a dose of 0.8 mg/kg, also formulated as a solution for injection.

Efficacy will be evaluated primarily by measuring overall survival (OS), defined as the time from randomisation to death from any cause. Secondary efficacy assessments will include progression free survival (PFS), determined by the interval from randomisation to documented disease progression or death, and patient‑reported health‑related quality of life (HRQoL), captured through validated patient‑reported outcome questionnaires. Additional secondary endpoints will comprise the incidence, seriousness, and relationship of adverse events, vital‑sign measurements, and clinical laboratory results; patterns of planned and unplanned hospital admissions, intensive‑care unit stays, emergency‑room visits, outpatient visits, and telephone contacts; and metrics of exposure to the trial medicinal products and treatment duration. All efficacy parameters will be collected according to the schedule outlined in the domain‑specific appendices and analysed using appropriate statistical methods consistent with the core outcome set for haematological conditions.