None listed
Conditions
Brief summary
This research project forms part of the RATIONAL Platform Trial. This study is being conducted to find out if patients with blood cancers receiving immunoglobulin for the purpose of preventing infections can safely stop after six months of therapy, and take oral antibiotics instead to prevent serious infections. The study will also test if the oral antibiotics should be taken every day or only as soon as an infection starts. 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 three groups (arms) to compare the different treatments. There is one usual care group and two investigational groups. The three groups are: 1. Continue receiving immunoglobulin (IVIg or SCIg) – this is the usual care group. 2. Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to take every day. 3. Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to keep at home to use as soon as symptoms of an infection develop. Each participant has a one in three chance of being in each group. Each participant has a two in three chance of receiving oral antibiotics. Half of the participants receiving oral antibiotics will be asked to taken them every day, the other half will be asked to take them only if symptoms of infection develop. 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: Stop Immunoglobulin (Ig) and commence prophylactic oral antibiotics. - Once daily trimethoprim-sulfamethoxazole (co-trimoxazole), oral tablet, 160mg/800mg. Nb: Doxycycline 100mg daily as an alternative for participants 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 Ig, or discontinued from their assigned trial treatment. Arm B: Stop Immunoglobulin without commencement of prophylactic oral antibiotics. - Participants will be prescribed amoxycillin/clavulanic acid, oral tablet, 1750-2000mg/250mg, and ciprofloxacin, oral tablet, 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 of Arm A and Arm B Intervention: 12 months. If a participant on Arm A or Arm B experiences a Grade 3 or higher infectious complication, they may recommence Ig replacement, as directed by their treating clinician. The treating clinician may discontinue participants from their assigned treatment if continued participation is no longer in the participant's best interest. If a participant is discontinued from their assigned treatment, participation in the trial will not end. Trial follow-up and data collection will continue for the remaining time of the 12-month intervention period. Participants will be asked to complete a daily study diary to monitor oral antibiotic use and adherence to the interventions.
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 Stop-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Stop-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 Stop-Ig domain 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. Willing and able to comply with each of the treatment arms.
Exclusion criteria
Patients are eligible for the Stop-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Stop-Ig domain. RATIONAL-PT exclusion criteria: 1. Treating team deems enrolment in the study is not in the best interests of the patient Stop-Ig domain 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 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 (e.g. living long distance from medical facility) that are likely to limit a 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 <30mL/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.
Outcome results
None listed