Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Immunoglobulin Stopping or Extension (Stop Ig)

Not Applicable

Recruiting

• Conditions: Myeloma; Leukemia; Non Hodgkin's Lymphoma
• Interventions: Drug: Trimethoprim Sulfamethoxazole; Drug: Amoxycillin/clavulanic acid; Biological: Immune Globulin Intravenous

• Registration Number: NCT07202091
• Lead Sponsor: Monash University

Brief Summary

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.

Detailed Description

This is a domain within the RATIONAL Platform Trial to test the effectiveness and safety of stopping Ig replacement with or without prophylactic antibiotics compare to continuing Ig replacement.

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. Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for at least 6 consecutive months.
2. Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator.
3. Patient is willing and able to comply with each of the treatment arms.

Exclusion Criteria

1. Prior or planned allogeneic haematopoietic stem cell transplantation.
2. Major infection (Grade 3 or higher) in preceding 3 months, and/or current active infection requiring systemic antimicrobial treatment.
3. Already receiving systemic antibiotic prophylaxis for the purpose of preventing bacterial infection (NB: patients may receive antiviral, antifungal and PJP prophylaxis).
4. Intolerance of all trial antibiotic options in either arm A or arm B.
5. Communication, compliance or logistical issues that are likely to limit patient's ability to take prophylactic or emergency antibiotics, or to obtain urgent medical attention for symptoms of infection.
6. Pregnant or breastfeeding.
7. Severe renal impairment (estimated or measured creatinine clearance of < 30 mL/min).
8. Previous splenectomy.
9. Previous participation in this domain.
10. Treating team deems enrolment in the domain is not in the best interests of the patient.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Stop Ig and commence prophylactic oral antibiotics	Trimethoprim Sulfamethoxazole	Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. NB: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.
Arm B: Stop Ig	Amoxycillin/clavulanic acid	Patients will be provided with amoxycillin/clavulanic acid 1750-2000mg/250mg and ciprofloxacin 750 mg to keep at home for initial use if symptoms of infection develop, with immediate review by their treating clinical team, or nearest emergency department or medical practitioner with phone contact to treating team if most practical. NB: Clindamycin 600 mg is permitted as an alternative to amoxycillin/clavulanic acid for patients with hypersensitivity to penicillin. Ciprofloxacin is omitted for participants with hypersensitivity.
Arm C: Continue Ig	Immune Globulin Intravenous	Participants will continue treatment with their current Ig replacement schedule. Participants will receive monthly (every 4 weeks ± 1 week) intravenous immunoglobulin at a dose of 0.4g/kg, modified to achieve an IgG trough level of at least lower limit of age-specific serum IgG reference range. For patients who have already had their Ig dose titrated to IgG trough level, they may continue on their current monthly dose of Ig replacement. SCIg, weekly, may be used in patients who meet local criteria for home-based self-administration in centres with established SCIg programs. Dosing is usually given at 100mg/kg/week, modified to achieve an IgG steady state level of at least the lower limit of the serum reference range.

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).	Occurrence of one or more treatment-related adverse events.
Number of treatment-related adverse events.	12 months following randomisation (or, in domains with a single treatment arm, time from registration.	Number of treatment-related adverse events.
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 different 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 different 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