Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension (RATIONALISE)
Haematological Malignancy, Hypogammaglobulinemia
About this trial
This is an interventional treatment trial for Haematological Malignancy focused on measuring Myeloma, Lymphoma, Leukaemia, Blood cancer, Malignancy, Infection, Antibiotic, Anti-infective agent, Immunoglobulin
Eligibility Criteria
Inclusion Criteria: Aged greater than or equal to 18 years of age Diagnosis of chronic lymphocytic leukaemia (CLL), multiple myeloma (MM) or non-Hodgkin lymphoma (NHL). Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for longer than 6 consecutive months. Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator. Life expectancy greater than 12 months. Able to give informed consent, and willing and able to comply with each of the treatment arms. Exclusion Criteria: Prior or planned allogeneic haematopoietic stem cell transplantation. Major infection (Grade 3 or higher) in preceding 3 months, and/or current active infection requiring antimicrobial treatment. Already receiving daily antibiotic prophylaxis for the purpose of preventing bacterial infection (Note: patients may receive antiviral, antifungal and Pneumocystis jirovecii pneumonia (PJP) prophylaxis). Intolerance of all trial antibiotic options in either arm A or arm B. 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. Pregnant or breastfeeding. Severe renal impairment (estimated or measured creatinine clearance of less than 30 mL/min). Previous splenectomy. Previous participation in this trial. Treating team deems enrolment in the study is not in the best interests of the patient.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
ARM A: Stop immunoglobulin (Ig) and commence prophylactic oral antibiotics
ARM B: Stop immunoglobulin (without prophylactic antibiotics)
ARM C: Continue immunoglobulin
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
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
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.