None listed
Conditions
Brief summary
This research project forms part of the RATIONAL Platform Trial. 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. While immunoglobulin is commonly used long term in patients with blood cancer, we don’t know whether oral antibiotics are just as good at preventing serious infections. The research project is investigating using oral antibiotics (in tablet form) to determine if they are as effective as IVIg or SCIg in reducing the risk of infections in people with blood cancers. Who’s it for? Patients with a blood cancer and low levels of certain antibodies (immunoglobulins) in the blood. Your treating doctor will check your eligibility to participate in this study. You will need to undergo screening assessments to find out if it is safe for you to be involved in the study. Study details: In this clinical trial domain, participants will be divided into two groups (arms) to compare the different treatments. There is one usual care group and one investigational group. The two groups are: 1. Start immunoglobulin (IVIg or SCIg) replacement therapy. 2. Start oral antibiotics to take every day. Each participant is put into a group by chance (randomly). If eligible to participate in a domain of the RATIONAL-PT, your active study participation in that domain will last for 13 months and all participants will return to the hospital for a study visit every 3 months (4 more in-person visits after Day 1). During each month of the 12-month treatment period except the months in which you are attending in-person study visits, you will receive a phone call from your treating clinical team to check your progress (8 calls in total). Even if you are recommended to, or choose to, stop your domain treatment during the 12-month treatment period, you will be asked to continue attending study visits and having phone calls until the end of the trial period (13 months in total) because we are still interested in your outcomes. At the end of your participation on the study, your doctor will decide if you still require treatment to prevent infection, and if you do, whether to continue on the treatment you received during the study (immunoglobulins, antibiotics or none). The results of this trial will inform clinical decision making about the use of immunoglobulin and oral antibiotics for patients with blood cancers. Your participation may help doctors who treat patients with blood diseases in the future to know whether to prescribe oral antibiotics or immunoglobulins to try to prevent the onset of serious infections.
Interventions
Arm A: Start prophylactic oral antibiotics:
- Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Nb: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.
- Dose adjustments: If a participant has cytopenia or renal impairment a 50% dose reduction may be made depending on the cause and/or severity of the cytopenia or renal impairment. Participants may be switched to the alternative antibiotic or discontinued from their assigned tria
Arm A: Start prophylactic oral antibiotics: - Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Nb: Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole. - Dose adjustments: If a participant has cytopenia or renal impairment a 50% dose reduction may be made depending on the cause and/or severity of the cytopenia or renal impairment. Participants may be switched to the alternative antibiotic or discontinued from their assigned trial treatment. - If a participant experiences a serious adverse event or serious infectious complication, the local Investigator may choose to discontinue the participant from their assigned trial treatment if it is no longer in the participant’s best interest. In these cases, the participant may recommence immunoglobulin replacement therapy as directed by their treating clinician. - Adherence to the intervention will be assessed via review of a study diary completed by the participants. Duration of Intervention: 12 months.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients are eligible for the Start-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Start-Ig domain. RATIONAL-PT inclusion criteria: 1. Aged greater than or equal to 18 years of age 2. Diagnosis of haematological malignancy, including Chronic Lymphocytic Leukaemia (CLL), Multiple Myeloma (MM) or Non-Hodgkin's Lymphoma (NHL) 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 Start-Ig domain inclusion criteria: None.
Exclusion criteria
Patients are eligible for the Start-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Start-Ig domain. RATIONAL-PT exclusion criteria: 1. Treating team deems enrolment in the study is not in the best interests of the patient Start-Ig domain exclusion criteria: 1. Prior or planned allogeneic haematopoietic stem cell transplantation. 2. Already receiving systemic antibiotic prophylaxis for the purpose of preventing bacterial infection (NB: patients may receive antiviral, antifungal and Pneumocystis jirovecii Pneumonia (PJP) prophylaxis). 3. Received immunoglobulin replacement in the preceding three months. 4. Objection to receiving immunoglobulin products. 5. Known history of IgA deficiency with anti-IgA. 6. History of severe allergy to immunoglobulin products. 7. Current active infection requiring systemic antibiotics. 8. Allergy or intolerance of all domain antibiotic options. 9. Pregnant or breastfeeding. 10. Severe renal impairment (estimated or measured creatinine clearance of < 30 mL/min). 11. Previous splenectomy. 12. Previous participation in this domain. 13. Treating team deems enrolment in the domain is not in the best interest of the patient.
Outcome results
None listed