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

Official title

A Multicentre, Adaptive, Randomised, Multidomain, Platform Trial for Dose Optimization in the Treatment of Adult Patients With Haematological Diseases (BLOOD-dose): Core Protocol

Overview

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.

Detailed description

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.

Interventions

• Drug teclistamab OR talquetamab OR elranatamab OR linvoseltamab
  ElasTEC: A phase 4, open-label, parallel-group, two-arm domain on the BLOOD-dose platform trial to evaluate the non-inferiority, safety, and effectiveness of reduced-frequency bispecific antibody treatments (teclistamab, talquetamab, elranatamab and linvoseltamab) compared with standard-frequency treatment in patients with relapsed/refractory multiple myeloma.
• Drug BTK inhibitors (ibrutinib and zanubrutinib)
  BELLIS: A phase 4, open-label, parallel-group, two-arm domain to assess the effectiveness and safety of reduced-dose BTK inhibitors (ibrutinib and zanubrutinib) compared to standard-dose in male and female patients with Waldenström´s macroglobulinemia

Primary outcome measures

• Overall survival [Time frame: OS is defined as the time from randomization until the time of death due to any cause, assessed up to 5 years.]

Secondary outcome measures (5)

• Progression free survival [Time frame: PFS is defined as the time from randomization until clinical progression or death from any cause, assessed up to 5 years.]
• Patient-reported health-related quality of life [Time frame: 1 year]
• Number of Participants with Treatment Emergent Adverse Events as Assessed by CTCAE v6.0 [Time frame: Through study completion, an average of 1 year]
• Hospital Admission [Time frame: From Time of randomization to end of follow-up, assessed up to 2 years.]
• Cost of intervention [Time frame: From first dose to last recorded date of dosing OR From randomization to last recorded date of dosing or end of study, whichever occurs first, assessed up to 2 years.]

Eligibility criteria

Inclusion criteria

• Participants of any sex who are at least 18 years of age at the time of providing informed consent.
• Participant diagnosed with a haematological disease, i.e. any disorder that primarily affects the blood, bone marrow, the lymphatic system and/or blood-forming organs.
• Should be eligible for participation in at least one of the currently active domains.
• Capable of giving signed informed consent for each applicable DSA(s). By consenting to a domain, participants also consent to participation in BLOOD-dose.

Exclusion criteria

• The participant tient is expected to live less than 3 months, as judged by the investigator.
• Any condition that, in the opinion of the investigator, impairs the participant's ability to understand trial procedures, provide informed consent and/or interfere with participation and/or compliance in the trial.

Domain eligibility criteria: each domain has its own specific eligibility criteria detailed in each DSA.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 5 centers

• Copenhagen University Hospital - Rigshospitalet — Copenhagen
• Aalborg University Hospital — Aalborg
• Aarhus University Hospital — Aarhus
• Odense University Hospital — Odense
• Roskilde University Hospital — Roskilde

Publications

• Tannock IF, de Vries EGE, Fojo A, Buyse M, Moja L. Dose optimisation to improve access to effective cancer medicines. Lancet Oncol. 2025 Mar;26(3):e171-e180. doi: 10.1016/S1470-2045(24)00648-X. PMID 40049207

Identifiers

NCT: NCT07474961 · p-2026-20598 · 2026-525658-13-00 · U1111-1334-9059

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗