BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases.

Multiple Myeloma, Waldenstrom Macroglobulinaemia

Multiple Myeloma, Platform Trial, Waldenstrom Macroglobulinaemia, Dose-optimization

BLOOD-dose is a multicentre, adaptive, randomized, multidomain platform trial designed to optimize treatment dosing strategies in adult patients with haematological diseases. The BLOOD-dose core protocol outlines the overall clinical trial design that applies to all included interventions, while domain-specific appendices (DSA) detail the unique characteristics of each domain and specify domain-specific interventions. New domains will be incorporated over time to address distinct dose-optimization research questions across different haematological conditions and interventions.

Background: Approved dosing regimens in haematology are largely derived from clinical trials conducted in relatively homogeneous patient populations, which may not reflect the diversity encountered in routine clinical practice. Many new anticancer and haematological treatments are developed using early phase trial designs that define dose selection primarily based on dose-limiting toxicity, often aiming to establish a maximum tolerated dose. While this approach supports regulatory approval, it may not identify the optimal biological or clinically effective dose for long-term treatment. This uncertainty may contribute to overtreatment, increased toxicity, impaired quality of life, and unnecessary healthcare costs. Furthermore, established long-term or life-long treatment regimens represent important opportunities for dose optimization, especially as therapeutic strategies and patient needs evolve over time. Platform trials provide an efficient framework to evaluate multiple interventions within a single disease area under a unified master protocol. In domain-based platform trials, interventions are grouped into predefined domains, enabling efficient comparisons, rapid progress, and the addition of new research domains over time. Objectives: The BLOOD-dose platform trial aims to determine the optimal treatment intensity for patients with haematological diseases. Due to disease heterogeneity, objectives, endpoints, and estimands will vary across domains. Outcomes: Given the heterogeneity of haematological diseases, objectives, endpoints, and estimands will differ across domains. A core outcome set (COS) comprising 6 core outcome measurements has been established through a Delphi consensus process. Each domain is expected to include at least one core outcome measure as its primary endpoint, with all other core outcomes included as secondary endpoints. Design: BLOOD-dose is an investigator-initiated, multicentre, adaptive, randomized, multidomain platform trial. Domains and interventions: Interventions across different haematological diseases will be defined in domain-specific appendices that will be amended over time. Eligibility: In addition to meeting the core protocol eligibility criteria, participants must also meet the domain-specific eligibility criteria for at least one domain.

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