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

Monash University

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Non Hodgkin's Lymphoma; Myeloma; Leukemia

Treatments: Drug: Trimethoprim Sulfamethoxazole; Drug: Amoxycillin/clavulanic acid; Biological: Immune Globulin Intravenous

Study type: Interventional

Funder types: Other

Identifiers

NCT07202091

TRU-RPT-22 Stop-Ig

Details and patient eligibility

About

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.

Full 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.

Enrollment: 900 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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900 participants in 3 patient groups

Arm A: Stop Ig and commence prophylactic oral antibiotics

Other group

Description:

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

Treatment:

Drug: Trimethoprim Sulfamethoxazole

Arm B: Stop Ig

Other group

Description:

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.

Treatment:

Drug: Amoxycillin/clavulanic acid

Arm C: Continue Ig

Other group

Description:

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.

Treatment:

Biological: Immune Globulin Intravenous