BANDICOOT: An Adaptive Platform Trial to Improve Health Outcomes After Paediatric Stem Cell Transplant

Official title

BANDICOOT: An Adaptive Platform Trial Designed to Improve the Complications, Cost-effectiveness and Health Outcomes for Children Receiving a Stem Cell Transplant

Overview

Background: In children with \>120 rare diseases, haematopoietic stem cell transplant (HSCT) provides a medical "reset" for the body, replacing diseased or dysfunctional bone marrow with healthy donor-derived stem cells following high-dose chemotherapy and/or radiotherapy. However, severe and fatal complications are common with HSCT. There has been a lack of properly conducted clinical trials to decrease mortality and morbidity. Traditional randomised controlled trials (RCTs) have several critical limitations in children undergoing HSCT, including population heterogeneity, restrictive eligibility criteria and slow enrolment. Adaptive platform trials (APTs) may overcome these limitations through enhanced trial efficiency by sharing a control group, reducing sample size and allowing continuous learning from accumulating data. APTs also allow simultaneous evaluation of distinct interventions at different timepoints and in multiple subgroups of participants, facilitating tailored approaches across heterogeneous populations. When an intervention proves superior, it becomes the new standard of care, allowing additional interventions to be introduced. To improve outcomes, we have developed an international APT - BANDICOOT. This trial will continuously enrol children and adolescents receiving HSCT and allow the assessment of multiple novel interventions simultaneously. The goal is to accelerate research findings, reduce duplication of efforts, and improve patient outcomes. Objectives: The primary objective of BANDICOOT is to determine the effectiveness of a range of interventions to improve HSCT outcomes for children and adolescents. The secondary objectives include: * Assessing the cost-effectiveness of trial interventions * Assessing the safety of a range of interventions to improve HCT outcomes * Collection of a core data set for participants consenting to the platform regardless of domain eligibility. Study design: BANDICOOT is a prospective, pragmatic, adaptive platform trial with interventions organised into domains. Domains may be open-label or blinded. Study population: The trial population will be children aged 1-week old to 18 years old who are receiving an HSCT. Trial outcomes: The primary outcome is an ordinal scale of HSCT outcomes based on organ support, viraemia, immune reconstitution and relapse status censored at Day 100 post HSCT. The selection and grading of components within this ordinal endpoint was informed by a formal endpoint development process, described in detail by Walker et al, 2025 (see References). Interventions: Multiple interventions will be evaluated in BANDICOOT across multiple treatment modalities (domains). New interventions will be added over time, and interventions may be dropped for futility or included in standard care as the study progresses. The details of the interventions will be provided in separate clinicaltrials.gov Study Records, linked to this Master record. Abbreviated methods: Inferences in this trial will be based on a Bayesian statistical model. The primary outcome will be analysed using a multinomial model with a cumulative logistic link, which is an extension of a binary logistic model to account for ordinal outcomes with more than two categories, and is commonly known as the 'proportional odds' model. Secondary outcomes will be analysed with parametric models specific to the type of outcome (e.g., the Bernoulli model with a logistic link for binary endpoints).

Interventions

• Other Standard care
  Participants enrolled in the BANDICOOT platform will receive standard care unless eligible for and enrolled in a domain. Domain interventions and eligibility will be described separately in linked Study Records.

Primary outcome measures

• Number of participants enrolled in the BANDICOOT Platform [Time frame: From platform activation through to platform closure (anticipated 20 years)]

Eligibility criteria

Inclusion criteria

• Aged >1 week to ≤ 18 years old
• The participant is intending to receive or will be eligible for allogeneic HSCT within the next 4 months.

Exclusion criteria

• Death is deemed to be imminent and inevitable AND one or more of the participant or parent/substitute decision maker, or attending physician are not committed to full active treatment
• A suitable donor for HCT is not identified.

Each domain may have additional, domain-specific eligibility criteria. The additional eligibility criteria that are specific to a domain will be provided in each domain-specific Study Record, linked to this Master record. Participants who fulfil the BANDICOOT Platform Eligibility Criteria will be assessed for enrolment into all domains that are active at their trial site.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Walker H, McLeman L, Meyran D, Goh LY, Summers P, Stolper J, Hanna D, Hughes D, Wang S, Toro C, Williams E, Dyas R, Rubinek LC, Taylor K, Selman CJ, Grobler A, Lee KJ, Snelling T, Cole T, Gwee A, Conyers R. Co-designing a Novel Ordinal Endpoint for an Adaptive Platform Trial, BANDICOOT, in Pediatric Hematopoietic Stem Cell Transplant. Transplant Cell Ther. 2025 May;31(5):321.e1-321.e12. doi: 10.10 PMID 39921207

Identifiers

NCT: NCT07679100 · 128474

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗