Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Platform Trial (RATIONAL-PT)
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorMonash University
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged greater than or equal to 18 years of age
Diagnosis of haematological malignancy, including (CLL) chronic lymphocytic leukemia, (MM) multiple myeloma or (NHL) non-Hodgkin's lymphoma.
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)
Life expectancy > 12 months
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
Intravenous immunoglobulin
Biological/Vaccine(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.
Trimethoprim / Sulfamethoxazole
DrugOnce daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.
Amoxicillin clavulanic acid
DrugPatients 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.
Intravenous immunoglobulin (IVIG)
Biological/VaccineArm 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.
Treatment groups
900 Participants
are divided into 3 treatment groupsGroup A: Start ImmunoglobulinOther 2 interventions
Group B: Stop ImmunoglobulinOther 3 interventions
Group C: Dose ImmunoglobulinOther 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
12 months following randomisation (or, in domains with a single treatment arm, time from registration)Secondary outcomes
1
Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months
Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months
Time frame
12 months following randomisation (or, in domains with a single treatment arm, time from registration)2
Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.
Time frame
12 months following randomisation (or, in domains with a single treatment arm, time from registration)3
Number of 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.
Time frame
12 months following randomisation (or, in domains with a single treatment arm, time from registration)4
Occurrence of one or more microbiologically documented infections from randomisation to 12 months.
Occurrence of one or more microbiologically documented infections from randomisation to 12 months.
Time frame
12 months following randomisation (or, in domains with a single treatment arm, time from registration)Sponsors and contacts
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Source ClinicalTrials.gov