Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension

NCT ID: NCT05678621

Last Updated: 2024-04-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-30

Study Completion Date

2027-04-30

Brief Summary

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The aim of the study is to find out if patients with blood cancers receiving immunoglobulin (Ig) for the purpose of preventing infections can safety stop immunoglobulin after six months of therapy, and take oral antibiotics instead to prevent serious infections.

Patients may be eligible to join this study if they are aged 18 years or above, have an acquired hypogammaglobulinaemia secondary to a haematological malignancy, and have been receiving intravenous or subcutaneous Ig for longer than 6 consecutive months.

Participants will be randomised (allocated by chance) to one of three treatment groups, as follows:

* Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to take every day (ARM A)
* Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to keep at home to use as soon as symptoms of an infection develop (ARM B)
* Continue receiving immunoglobulin (IVIg or SCIg) - this is the usual care group (ARM C)

The duration of each treatment is for 12 months from study entry.

Participants will be asked to attend a screening/baseline visit so that their treating clinician can assess their eligibility for the trial and collect baseline data. If eligible for the trial, participants will then be randomly allocated to one of the three treatment groups.

Once randomised, active participation in the study will last for 13 months. During this period, participants will be asked to return to the hospital for a study visit every 3 months, with monthly telephone visits to check-in on your progress between each in-person visit. Participants will also be asked to complete a study diary, recording treatment compliance and signs/symptoms of infection experienced throughout the study period.

Types of assessments and data collected will include: Medical history, demographics, physical examination, blood tests, stool sample, quality of life questionnaires, information about your general health, hospitalisations, medications and procedures. In order to assess and compare the cost-effectiveness of the treatment groups, the study team will also request authorisation from participants to access their Medicare Benefits Schedule (MBS), Pharmaceutical Benefits Scheme (PBS), and Australian Immunisation Register (AIR) data.

Detailed Description

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Conditions

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Haematological Malignancy Hypogammaglobulinemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Infectious outcomes and adverse events will be adjudicated by an independent, blinded outcome adjudication committee.

Study Groups

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ARM A: Stop immunoglobulin (Ig) and commence prophylactic oral antibiotics

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

Duration: 12 months. Route: PO

Group Type EXPERIMENTAL

trimethoprim-sulfamethoxazole (co-trimoxazole)

Intervention Type DRUG

Doxycycline is an alternative for participants with hypersensitivity to co-trimoxazole.

ARM B: Stop immunoglobulin (without prophylactic antibiotics)

Participants will be prescribed 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 participants with hypersensitivity to penicillin.

Duration: 12 months. Route: PO

Group Type EXPERIMENTAL

amoxycillin/clavulanic acid and ciprofloxacin

Intervention Type DRUG

clindamycin is an alternative to amoxycillin/clavulanic acid for participants with hypersensitivity to penicillin.

ARM C: Continue immunoglobulin

Participants will continue treatment with their current Ig replacement schedule. Participants will receive either Intravenous Ig (IVIg) or Subcutaneous Ig (SCIg)

* IVIg: Participants will be treated in accordance with the Criteria for Clinical Use of Immunoglobulin in Australia. Monthly (every 4 weeks ± 1 week) dose of 0.4g/kg, modified to achieve an Immunoglobulin G (IgG) trough level of at least lower limit of age-specific serum IgG reference range. In the first month of therapy, if IgG \<4g/L then an additional (loading) dose of 0.4g/kg may be given at the clinician's discretion.
* SCIg: Subcutaneous immunoglobulin weekly may be used in patients who meet local criteria for home based self-administration in centres with established SCIg programs. A loading IVIg dose may be given in the first month if required. Thereafter, dosing at 100mg/kg/week, modified to achieve an IgG steady state level of at least the lower limit of the serum reference range.

Duration: 12 months.

Group Type ACTIVE_COMPARATOR

Immunoglobulins

Intervention Type DRUG

Intravenous monthly immunoglobulin or subcutaneous weekly immunoglobulin

Interventions

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trimethoprim-sulfamethoxazole (co-trimoxazole)

Doxycycline is an alternative for participants with hypersensitivity to co-trimoxazole.

Intervention Type DRUG

amoxycillin/clavulanic acid and ciprofloxacin

clindamycin is an alternative to amoxycillin/clavulanic acid for participants with hypersensitivity to penicillin.

Intervention Type DRUG

Immunoglobulins

Intravenous monthly immunoglobulin or subcutaneous weekly immunoglobulin

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Aged greater than or equal to 18 years of age
2. Diagnosis of chronic lymphocytic leukaemia (CLL), multiple myeloma (MM) or non-Hodgkin lymphoma (NHL).
3. Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for longer than 6 consecutive months.
4. Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator.
5. Life expectancy greater than 12 months.
6. Able to give informed consent, and 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 antimicrobial treatment.
3. Already receiving daily antibiotic prophylaxis for the purpose of preventing bacterial infection (Note: patients may receive antiviral, antifungal and Pneumocystis jirovecii pneumonia (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 less than 30 mL/min).
8. Previous splenectomy.
9. Previous participation in this trial.
10. Treating team deems enrolment in the study is not in the best interests of the patient.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Monash University

OTHER

Sponsor Role lead

Responsible Party

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Erica Wood

Professor Erica Wood, Head, Transfusion Research Unit, Public Health and Preventive Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Prof Erica Wood

Role: PRINCIPAL_INVESTIGATOR

Monash University

Prof Zoe McQuilten

Role: PRINCIPAL_INVESTIGATOR

Monash University

Locations

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Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status NOT_YET_RECRUITING

Concord Hospital

Concord, New South Wales, Australia

Site Status RECRUITING

Royal North Shore

St Leonards, New South Wales, Australia

Site Status NOT_YET_RECRUITING

Monash Medical Centre

Clayton, Victoria, Australia

Site Status RECRUITING

Austin Hospital

Heidelberg, Victoria, Australia

Site Status RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Sunshine Hospital

St Albans, Victoria, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Prof Zoe McQuilten

Role: CONTACT

+61 3 9903 0379

Other Identifiers

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TRU-RLS-21

Identifier Type: -

Identifier Source: org_study_id

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