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

NCT07202091 | Recruiting Phase 2 DMC

• 1 other identifier: TRU-RPT-22 Stop-Ig
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 3

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.

Conditions

Myeloma; Leukemia; Non Hodgkin's Lymphoma

Keywords

immunoglobulin; antibiotics; myeloma; leukaemia; lymphoma; non Hodgkins; infection; infections; blood; cancer; haematology

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS).

  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.

  12 months following randomisation (or, in domains with a single treatment arm, time from registration).

Secondary Outcomes (14)

• 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 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).

• 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).

• 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).

• 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).

Study Arms (3)

Arm A: Stop Ig and commence prophylactic oral antibiotics

OTHER

Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. NB: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.

Drug: Trimethoprim Sulfamethoxazole

Arm B: Stop Ig

OTHER

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.

Drug: Amoxycillin/clavulanic acid

Arm C: Continue Ig

OTHER

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.

Biological: Immune Globulin Intravenous

Interventions

Trimethoprim Sulfamethoxazole DRUG

Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. NB: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.

Also known as: Co-Trimoxazole

Arm A: Stop Ig and commence prophylactic oral antibiotics

Amoxycillin/clavulanic acid DRUG

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.

Also known as: Ciprofloxacin

Arm B: Stop Ig

Immune Globulin Intravenous BIOLOGICAL

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.

Also known as: Immune Globulin Subcutaneous

Arm C: Continue Ig

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Prior or planned allogeneic haematopoietic stem cell transplantation.
• Major infection (Grade 3 or higher) in preceding 3 months, and/or current active infection requiring systemic antimicrobial treatment.
• Already receiving systemic antibiotic prophylaxis for the purpose of preventing bacterial infection (NB: patients may receive antiviral, antifungal and PJP prophylaxis).
• Intolerance of all trial antibiotic options in either arm A or arm B.
• 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.
• Pregnant or breastfeeding.
• Severe renal impairment (estimated or measured creatinine clearance of \< 30 mL/min).
• Previous splenectomy.
• Previous participation in this domain.
• Treating team deems enrolment in the domain is not in the best interests of the patient.

Sponsors & Collaborators

• Monash University: lead

Study Sites (3)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Austin Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Northern Health

Melbourne, Victoria, 3004, Australia

RECRUITING

Related Links

• Study Website

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Leukemia; Lymphoma; Infections; Neoplasms

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; Amoxicillin-Potassium Clavulanate Combination; Ciprofloxacin; gamma-Globulins

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zoe McQuilten, Professor

  Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: An independent outcome adjudication committee will meet to review and adjudicate infection outcome data. These committee members will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Up to 900 participants will be recruited to the RATIONAL-PT, including up to 300 per domain. The aim of the platform is to determine optimal supportive care interventions for patients with haematological malignancies. The primary outcome for the platform is Event-free survival (EFS), 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. Data from each domain will contribute to the primary analysis.

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: October 1, 2025
• Study Start: May 6, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)