Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Platform Trial (RATIONAL-PT)

Not Applicable

Recruiting

• Conditions: Myeloma; Non-Hodgkin's Lymphoma; Leukemia
• Interventions: Biological: Intravenous immunoglobulin; Biological: Intravenous immunoglobulin (IVIG); Drug: Trimethoprim / Sulfamethoxazole; Drug: Amoxicillin clavulanic acid

• Registration Number: NCT07202052
• Lead Sponsor: Monash University

Brief Summary

This is an adaptive platform study to find out how safe and effective different strategies are in comparison to each other, for preventing infection in patients with blood cancers.

It is a comparison between Immunoglobulin and antibiotics use.

Detailed Description

This study is being conducted to find out how safe and effective different strategies of infection prevention are in comparison to each other, for preventing infection in patients with blood cancers. The best way to find out this information is to directly compare the effect of different treatment strategies in patients with blood cancers. We want to know how these different treatments impact on your health and your use of healthcare services.

This research project uses an Adaptive Platform Design. This design allows the researchers to compare multiple infection prevention strategies within the same trial at the same time (rather than running separate trials), to analyse results as the trial occurs and to add new research questions during the course of the trial.

The treatments that you may receive as part of the study will be determined by which domain(s) of the platform you participate in. By combining data collected within each domain as part of the platform, the researchers can investigate and compare treatment strategies and infection outcomes across a broader range of participants.

Study Timeline

• Study Start: 2025-05-06
• Status Verified: 2025-06
• Study First Submitted: 2025-09-24
• Study First Submitted QC: 2025-09-24
• Last Update Submitted: 2025-09-24
• Study First Posted: 2025-10-01
• Last Update Posted: 2025-10-01
• Primary Completion: 2027-03-31
• Study Completion: 2027-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 900

Inclusion Criteria

1. Aged greater than or equal to 18 years of age
2. Diagnosis of haematological malignancy, including (CLL) chronic lymphocytic leukemia, (MM) multiple myeloma or (NHL) non-Hodgkin's lymphoma.
3. Eligible to receive or currently receiving Ig (IV or subcutaneous - SCIg) replacement for history of recurrent or severe infection(s) and IgG less than the lower limit of the reference range (excluding paraprotein) OR IgG<4g/L (excluding paraprotein)
4. Life expectancy > 12 months
5. Able to give informed consent

Exclusion Criteria

1. Treating team deems enrolment in the study is not in the best interests of the patient.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Start Immunoglobulin	Intravenous immunoglobulin	Patients eligible to start immunoglobulin are randomly assigned to: * receive either prophylactic antibiotic * or Ig replacement.
Start Immunoglobulin	Trimethoprim / Sulfamethoxazole	Patients eligible to start immunoglobulin are randomly assigned to: * receive either prophylactic antibiotic * or Ig replacement.
Stop Immunoglobulin	Intravenous immunoglobulin	Patients eligible to stop immunoglobulin are randomly assigned to: * Stop Ig and take daily antibiotics * Stop Ig and take antibiotics only when infections occur * Continue Ig therapy
Stop Immunoglobulin	Trimethoprim / Sulfamethoxazole	Patients eligible to stop immunoglobulin are randomly assigned to: * Stop Ig and take daily antibiotics * Stop Ig and take antibiotics only when infections occur * Continue Ig therapy
Stop Immunoglobulin	Amoxicillin clavulanic acid	Patients eligible to stop immunoglobulin are randomly assigned to: * Stop Ig and take daily antibiotics * Stop Ig and take antibiotics only when infections occur * Continue Ig therapy
Dose Immunoglobulin	Intravenous immunoglobulin (IVIG)	Patients receiving IVIg are randomly assigned to: * Continue with standard dose (0.4 g/kg) * Switch to a lower dose (0.25 g/kg)

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS)	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Defined as time from randomisation (or, in domains with a single treatment arm, time from registration) until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months
Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Occurrence of one or more microbiologically documented infections from randomisation to 12 months.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Occurrence of one or more microbiologically documented infections from randomisation to 12 months.
Number of microbiologically documented infections from randomisation to 12 months.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Number of microbiologically documented infections from randomisation to 12 months.
All-cause mortality at 12 months	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	All-cause mortality at 12 months
Infection-related mortality at 12 months	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Infection-related mortality at 12 months
Time free from hospitalisation with antimicrobial administration with therapeutic intent from randomisation to 12 months.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Time free from hospitalisation with antimicrobial administration with therapeutic intent from randomisation to 12 months.
Occurrence of one or more treatment-related adverse events	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	An adverse event includes any untoward medical occurrence that is not necessarily caused by the trial treatment. Examples of adverse events might include symptoms such as nausea, diarrhoea or headache.; Adverse events will be collected via clinical examination, hospital medical record, or self-report to study team or via study diary. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Relationship to treatment will be assessed by an Investigator at the trial site.
Number of treatment-related adverse events.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	An adverse event includes any untoward medical occurrence that is not necessarily caused by the trial treatment. Examples of adverse events might include symptoms such as nausea, diarrhoea or headache.; Adverse events will be collected via clinical examination, hospital medical record, or self-report to study team or via study diary. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Relationship to treatment will be assessed by an Investigator at the trial site.
Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months
Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated from randomisation to 12 months	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated from randomisation to 12 months
Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the questionnaire.	Randomisation, Month 3, Month 6, Month 9 and Month 12	Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the questionnaire.
Costs associated with allocated treatment arm and infections during study.	12 months following randomisation (or, in domains with a single treatment arm, time from registration)	Costs of infections and trial interventions will be estimated based on trial treatment and adverse event data within the hospital medical record, as well as linked data obtained from the Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Immunisation Register (AIR). Data from the quality of life questionnaires will be used to calculate quality adjusted life years.

Trial Locations

Locations (3)

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Austin Hospital; 🇦🇺 Melbourne, Victoria, Australia

Northern Health; 🇦🇺 Melbourne, Victoria, Australia