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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM A: Stop immunoglobulin (Ig) and commence prophylactic oral antibiotics | Experimental | 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 |
|
| ARM B: Stop immunoglobulin (without prophylactic antibiotics) | Experimental | 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 |
|
| ARM C: Continue immunoglobulin | Active Comparator | Participants will continue treatment with their current Ig replacement schedule. Participants will receive either Intravenous Ig (IVIg) or Subcutaneous Ig (SCIg)
Duration: 12 months. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| trimethoprim-sulfamethoxazole (co-trimoxazole) | Drug | Doxycycline is an alternative for participants with hypersensitivity to co-trimoxazole. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-free survival (EFS), defined as time from randomisation until occurrence of a Grade 3 or higher infection (as defined by CTCAE Version 5), or death from any cause. | 12 months following randomisation |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of patients who develop at least 1 Grade 3 or higher infection(s) from randomisation to 12 months. | 12 months following randomisation | |
| Proportion of patients with one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Prof Zoe McQuilten | Contact | +61 3 9903 0379 | zoe.mcquilten@monash.edu |
| Name | Affiliation | Role |
|---|---|---|
| Prof Erica Wood | Monash University | Principal Investigator |
| Prof Zoe McQuilten | Monash University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Canberra Hospital | Not yet recruiting | Garran | Australian Capital Territory | 2605 | Australia | |
Individual participant data will not be publicly available. Data will only be presented as a whole, no individual data will be published or presented.
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Infectious outcomes and adverse events will be adjudicated by an independent, blinded outcome adjudication committee.
|
| amoxycillin/clavulanic acid and ciprofloxacin | Drug | clindamycin is an alternative to amoxycillin/clavulanic acid for participants with hypersensitivity to penicillin. |
|
| Immunoglobulins | Drug | Intravenous monthly immunoglobulin or subcutaneous weekly immunoglobulin |
|
| 12 months following randomisation |
| Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months. Data collected from medical records will inform this outcome measure. | 12 months following randomisation |
| Proportion of patients with one or more microbiologically documented bacterial infections. | 12 months following randomisation |
| Number of microbiologically documented bacterial infections. | 12 months following randomisation |
| Time free from hospitalisation and antimicrobials with therapeutic intent. | 12 months following randomisation |
| Proportion of patients with one or more treatment-related adverse events | 12 months following randomisation |
| Number of treatment-related adverse events. | 12 months following randomisation |
| Proportion of patients with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated. | 12 months following randomisation |
| Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated. | 12 months following randomisation |
| Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months | QoL will be assessed using the EORTC QLQ-C30 questionnaire. | Randomisation and 3, 6, 9 and 12 months following randomisation. |
| Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months | QoL will be assessed using the Functional Assessment of Cancer Therapy - Neutropenia (FACT-N) questionnaire. | Randomisation and 3, 6, 9 and 12 months following randomisation. |
| Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months | QoL will be assessed using the EQ-5D-5L questionnaire. | Randomisation and 3, 6, 9 and 12 months following randomisation. |
| Costs associated with allocated treatment arm and infections during study | Costs associated with each treatment arm with be aggregated into Australian dollars. Aggregate costs will be calculated based on the following data sources: medical records, infection-related hospitalisations (using unit costs based on unlinked data from the Victorian Admitted Episodes Dataset, Victorian Emergency Minimum Dataset and the Victorian Cost Data Collection), Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Immunisation Registry (AIR) data. | 12 months following randomisation |
| Cost effectiveness of the allocated treatment arm | Differences in costs and Quality Adjusted Life Years (QALYs) for each of the treatment arms will be aggregated into a cost effectiveness ratio. The following data sources will be used to calculate this outcome measure: the EORTC QLQ-C30 questionnaire will be used to calculate QALYS. Costs will be calculated based on the following data sources: medical records, infection-related hospitalisations (using unit costs based on unlinked data from the Victorian Admitted Episodes Dataset, Victorian Emergency Minimum Dataset and the Victorian Cost Data Collection), Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Immunisation Registry (AIR) data. | 12 months following randomisation |
| Trough IgG level at 3, 6, 9 and 12 months from baseline. | 3, 6, 9 and 12 months from baseline |
| Proportion of patients in immunoglobulin cessation treatment arms who restart Ig over 12 months. | 12 months following randomisation |
| Covid anti-spike protein levels at baseline, 3, 6, 9, and 12 months. | 3, 6, 9 and 12 months following baseline |
| Concord Hospital |
| Recruiting |
| Concord |
| New South Wales |
| 2139 |
| Australia |
| Royal North Shore | Not yet recruiting | St Leonards | New South Wales | 2065 | Australia |
| Monash Medical Centre | Recruiting | Clayton | Victoria | 3168 | Australia |
| Austin Hospital | Recruiting | Heidelberg | Victoria | 3084 | Australia |
| The Alfred Hospital | Recruiting | Melbourne | Victoria | 3004 | Australia |
| Sunshine Hospital | Recruiting | St Albans | Victoria | 3021 | Australia |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D000361 | Agammaglobulinemia |
| D054219 | Neoplasms, Plasma Cell |
| D008223 | Lymphoma |
| D007938 | Leukemia |
| D009369 | Neoplasms |
| D007239 | Infections |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001796 | Blood Protein Disorders |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D009370 | Neoplasms by Histologic Type |
| D007160 | Immunoproliferative Disorders |
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| ID | Term |
|---|---|
| D015662 | Trimethoprim, Sulfamethoxazole Drug Combination |
| D000658 | Amoxicillin |
| D019818 | Clavulanic Acid |
| D002939 | Ciprofloxacin |
| D007136 | Immunoglobulins |
| ID | Term |
|---|---|
| D013420 | Sulfamethoxazole |
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D014295 | Trimethoprim |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004338 | Drug Combinations |
| D004364 | Pharmaceutical Preparations |
| D000667 | Ampicillin |
| D010400 | Penicillin G |
| D010406 | Penicillins |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D002969 | Clavulanic Acids |
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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