Myeloma, Non-Hodgkin's Lymphoma, Leukemia
Conditions
Keywords
immunoglobulin, antibiotics, myeloma, leukaemia, lymphoma, non Hodgkins, infection, infections, blood, cancer, haematology
Brief summary
This is an adaptive platform study to find out how safe and effective different strategies are in comparison to each other, for preventing infection in patients with blood cancers. It is a comparison between Immunoglobulin and antibiotics use.
Detailed description
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.
Interventions
BIOLOGICALIntravenous immunoglobulin
(IVIg) intravenous immunoglobulin every 4 weeks ± 1 week at a dose of 0.4g/kg, modified to achieve an (IgG) immunoglobulin G trough level of at least lower limit of age-specific serum IgG reference range; or 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. A loading IVIg dose may be given in the first month if required.
Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.
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. 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.
BIOLOGICALIntravenous immunoglobulin (IVIG)
Arm A: Low dose (IgRT) immunoglobulin replacement therapy: Participants will be treated with intravenous immunoglobulin monthly (every 4 weeks ± 1 week) at a dose of 0.25g/kg. No dose adjustment for trough serum IgG levels is required. Arm B: Usual dose: Participants will be treated with intravenous immunoglobulin monthly (every 4 weeks ± 1 week) 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.
Sponsors
Monash University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
An independent outcome adjudication committee will meet to review and adjudicate infection outcome data. These committee members will be blinded to treatment allocation.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged greater than or equal to 18 years of age 2. Diagnosis of haematological malignancy, including (CLL) chronic lymphocytic leukemia, (MM) multiple myeloma or (NHL) non-Hodgkin's lymphoma. 3. Eligible to receive or currently receiving Ig (IV or subcutaneous - SCIg) replacement for history of recurrent or severe infection(s) and IgG less than the lower limit of the reference range (excluding paraprotein) OR IgG\<4g/L (excluding paraprotein) 4. Life expectancy \> 12 months 5. Able to give informed consent
Exclusion criteria
1\. Treating team deems enrolment in the study is not in the best interests of the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 treatment-related adverse events | 12 months following randomisation (or, in domains with a single treatment arm, time from registration) | An adverse event includes any untoward medical occurrence that is not necessarily caused by the trial treatment. Examples of adverse events might include symptoms such as nausea, diarrhoea or headache. Adverse events will be collected via clinical examination, hospital medical record, or self-report to study team or via study diary. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Relationship to treatment will be assessed by an Investigator at the trial site. |
| Number of treatment-related adverse events. | 12 months following randomisation (or, in domains with a single treatment arm, time from registration) | An adverse event includes any untoward medical occurrence that is not necessarily caused by the trial treatment. Examples of adverse events might include symptoms such as nausea, diarrhoea or headache. Adverse events will be collected via clinical examination, hospital medical record, or self-report to study team or via study diary. Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. Relationship to treatment will be assessed by an Investigator at the trial site. |
| 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 the 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 the 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. |
| 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. |
Countries
Australia
Outcome results
None listed