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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma; Waldenstrom Macroglobulinaemia
• Intervention / Treatment: Drug: teclistamab OR talquetamab OR elranatamab OR linvoseltamab; Drug: BTK inhibitors (ibrutinib and zanubrutinib)

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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Anne Louise Tølbøll Sørensen, Ass. Prof.; Phone Number: +45 35451864; Email: anne.louise.toelboell.soerensen@regionh.dk
• Study Contact Backup: Name: Troels Hammer, Ass. Prof.; Phone Number: +45 35455198; Email: troels.hammer@regionh.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg University Hospital
    • Contact: Marianne T Severinsen, Professor; Phone Number: +45 20 84 28 69; Email: m.severinsen@rn.dk
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
    • Contact: Maja Ø Vase, PhD; Phone Number: +45 21423108; Email: majavase@rm.dk
  • Odense, Denmark, 5000
    • Odense University Hospital
    • Contact: Casper N Strandholdt, MD; Phone Number: +4520541981; Email: casper.norgaard.strandholdt@rsyd.dk
  • Roskilde, Denmark, 4000
    • Roskilde University Hospital
    • Contact: Christian Poulsen, Ass. Prof.; Phone Number: +45 46 32 32 00; Email: cbpo@regionsjaelland.dk
  • Greater Copenhagen Area
    • Copenhagen, Greater Copenhagen Area, Denmark, 2100
      • Copenhagen University Hospital - Rigshospitalet
      • Contact: Troels Hammer, Ass. Prof.; Phone Number: + 4535455198; Email: troels.hammer@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard dose of teclistamab OR talquetamab OR elranatamab OR linvoseltamab; Standard dose of teclistamab OR talquetamab OR elranatamab OR linvoseltamab in patients with relapsed/refractory multiple myeloma	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.; Other Names: Tecvayli OR Talvey OR Elrexfio OR Lynozyfic
Experimental: Reduced dose of teclistamab OR talquetamab OR elranatamab OR linvoseltamab; Reduced frequency of teclistamab OR talquetamab OR elranatamab OR linvoseltamab in patients with relapsed/refractory multiple myeloma	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.; Other Names: Tecvayli OR Talvey OR Elrexfio OR Lynozyfic
Active Comparator: Standard-dose BTK inhibitors in patients with Waldenström´s macroglobulinemia; 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	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; Other Names: Imbruvica OR Brukinsa
Experimental: Reduced dose of BTK inhibitors in patients with Waldenström´s macroglobulinemia; 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	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; Other Names: Imbruvica OR Brukinsa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	To compare survival between the interventions. The interventions will be defined in the DSA. The end of period follow-up will be defined in the DSA.	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

Outcome Measure	Measure Description	Time Frame
Progression free survival	Clinical progression will be defined in the domain according to the disease being investigated. Clinical progression will be defined in the domain according to the disease being investigated. The end of follow-upperiod will be defined in the DSA.	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	Patient-reported health-related quality of life (HRQOL) will be measured with at least one of the following instruments: Mean change from baseline in the HRQOL score for EORTC QLQ-C30.	1 year
Number of Participants with Treatment Emergent Adverse Events as Assessed by CTCAE v6.0	Number of Participants With Treatment Emergent Adverse Events. AEs of interest will be specified in the DSA.	Through study completion, an average of 1 year
Hospital Admission	Rate of hospitalisation per 100-participant-patient years. The end of follow-up period will be defined in the DSA.	From Time of randomization to end of follow-up, assessed up to 2 years.
Cost of intervention	Exposure to trial medicinal products.	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.

Collaborators and Investigators

• Sponsor: Anne Louise Tølbøll Sørensen
• Investigators: Study Chair: Anne Louise Tølbøll Sørensen, Ass. Prof., Rigshospitalet, Denmark

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): December 1, 2036
• Study Completion (Estimated): December 1, 2036

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Myeloma; Platform Trial; Dose-optimization; Waldenstrom Macroglobulinaemia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Waldenstrom Macroglobulinemia; zanubrutinib; ibrutinib; talquetamab
• Other Study ID Numbers: p-2026-20598; 2026-525658-13-00 (Ctis); U1111-1334-9059 (Other Identifier: WHO UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The BLOOD-dose management committee owns the rights to all intellectual property and the combined data collected as part of BLOOD-dose; individual sites retain ownership of data collected at their specific sites.

An anonymised version of the final dataset for each domain may be shared with other researchers following a reasonable request (i.e., a research proposal outlining the objectives, methodologies, and plans for data usage) and subsequent approval by the platform and domain management committees.

Participants will be informed about the possibility of data sharing during the informed consent process.

Analysis code may be shared with other researchers after reasonable request and approval by the platform and domain management committee.

• IPD Sharing Time Frame: 15.01.2030 - 15.01.2055

IPD Sharing Access Criteria

An anonymised version of the final dataset for each domain may be shared with other researchers upon reasonable request. Requests should include a research proposal outlining the objectives, methodologies, and intended use of the data, and will be subject to review and approval by the platform and relevant domain management committees.

Data sharing will be conducted in accordance with the General Data Protection Regulation (GDPR) and all applicable national and international legislative and regulatory requirements governing the protection of personal data. Only fully anonymised data will be shared, and appropriate safeguards and data governance procedures will be applied to ensure compliance with data protection obligations.

The study protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), and analytical code may be made available upon request.

A webaddress for finding more information about the IPD sharing plan is not yet available

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No