RATIONAL Platform Trial
Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy - Platform Trial (RATIONAL-PT)
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RATIONAL-PT is conducted in collaboration with hospital sites across Australia, New Zealand and Canada.
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Some blood cancers, or the medications used to treat them, can lead to hypogammaglobulinemia (low levels of immunoglobulin [antibodies] in the blood), resulting in an increased risk of serious infection. To treat this condition, patients are often given immunoglobulin (antibodies) to prevent serious infection.
The platform trial aims to address evidence gaps in immunoglobulin (Ig) use and infection prevention in patients with blood cancer. In the platform trial this is examined through three domains - Start-Ig, Stop-Ig and Dose-Ig - each designed to examine a different question around the use of immunoglobulin replacement therapy or prophylatic antibiotics for infection prevention.
Why do we need a platform trial?
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Studies supporting immunoglobulin use were conducted 20-30 years ago and we do not know the effects of immunoglobulin given to patients in the context of newer anti-cancer treatments.
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There is variation in the international guidelines on when to administer immunoglobulin, and this is reflected in the different practice for immunoglobulin administration between different countries.
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The optimal duration of immunoglobulin use is not clearly defined. The international guidelines vary considerably in their recommendations for if and when to trial a cessation of immunoglobulin.
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Immunoglobulin is made from donated plasma, and it is expensive, so must be used wisely. The demand for immunoglobulin is also increasing, leading to increased challenges for meeting demand.
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There is some evidence to support the rationale for using prophylactic oral antibiotics to treat patients with acquired hypogammaglobulinemia but their use in this context needs to be properly evaluated.
Trial Overview
RATIONAL-PT is an adaptive platform trial enrolling participants with acquired hypogammaglobulinemia secondary to haematological malignancy (chronic lymphocytic leukaemia, multiple myeloma, or non-Hodgkin's lymphoma).​
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Start-Ig Domain
Eligible participants will be allocated on a 1:1 ratio to one of two treatment groups:
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Start immunoglobulin replacement therapy (IVIg or SCIg)
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Start daily prophylactic oral antibiotics
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Stop-Ig Domain (RATIONALISE)
Eligible participants will be allocated on a 1:1:1 ratio to one of three treatment groups:
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Stop immunoglobulin and commence daily prophylactic oral antibiotics
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Stop immunoglobulin, and prescribed antibiotics to keep at home to use immediately if symptoms of infection develop, with immediate review by treating clinician team, nears emergency department or medical practitioner
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Continue to receive intravenous or sub-cutaneous immunoglobulin as per current treatment regimen​
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Dose-Ig Domain
Eligible participants will be allocated on a 1:1 ratio to one of two treatment groups:
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Low dose intravenous immunoglobulin replacement
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Standard dose intravenous immunoglobulin replacement
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The primary outcome of the platform trial is event-free survival, defined from the date of randomisation until the earliest date of occurrence of Grade 3 or higher infection (as per CTCAE version 5) as reviewed by an Outcome Adjudication Committee, or death from any cause.
Sub-studies
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Health Economics Analysis
Led by Dr. Laura Fanning and Prof Dennis Petrie of the Centre of Health Economics at Monash University, a multi-faceted health-economic analysis will be conducted to assess the cost effectiveness of the platform trial interventions
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Qualitative Study​
​Led by Dr. Khai Li Chai and Dr Catriona Parker of the Transfusion Research Unit at Monash University, a qualitative study will explore patient perspectives on the use of immunoglobulin and oral antibiotics
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Biological Study
​Led by Prof Orla Morrissey of the Department of Infectious Diseases at Monash University, a biological study will be performed to examine immune function in this patient population. Blood and faecal samples will be collected and sent to a central lab for testing.
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Pharmacokinetic/Pharmacodynamic (PK/PD) Study
Led by Prof Jason Roberts of the Centre for Clinical Research at University of Queensland, a the PK/PD study will involve blood sample collection to analyse the time-course of immunoglobulin absorption and determine the relationship between immunoglobulin dose and its effects on the body. This sub-study will aid our understanding of how immunoglobulin works and the impact of different dosing strategies.
Find out more
For further information and all general platform-related enquiries, please contact the Monash University Project Team
Alternatively, comprehensive trial information, including participating hospital sites can be found on the
Australian New Zealand Clinical Trials Registry (ANZCTR)
RATIONAL Platform Core Protocol
RATIONAL Platform Start-Ig Domain Protocol
© 2025 RATIONAL Platform Trial & RATIONALISE Trial