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NCT Number: NCT07202052

Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy Platform Trial (RATIONAL-PT)

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.

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Key information

Conditions

Myeloma Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Infections Leukemia Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Non-Hodgkin's Lymphoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Royal Adelaide Hospital, Adelaide, South Australia, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Able to give informed consent

Exclusion criteria

  • Treating team deems enrolment in the study is not in the best interests of the patient.

Treatment and study plan

Intravenous immunoglobulin

Biological

(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.

Other names: Subcutaneous immunoglobulin

Trimethoprim / Sulfamethoxazole

Drug

Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.

Other names: co-trimoxazole

Amoxicillin clavulanic acid

Drug

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.

Other names: Ciprofloxacin

Intravenous immunoglobulin (IVIG)

Biological

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.

Primary outcomes

  1. Event-free survival (EFS)

    Time frame: 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 outcomes

  1. 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)

    Occurrence of at least one Grade 3 or higher infection(s) from randomisation to 12 months

  2. 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)

    Occurrence of one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.

  3. 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)

    Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) from randomisation to 12 months.

  4. 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)

    Occurrence of one or more microbiologically documented infections from randomisation to 12 months.

  5. Number of 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)

    Number of microbiologically documented infections from randomisation to 12 months.

  6. All-cause mortality at 12 months

    Time frame: 12 months following randomisation (or, in domains with a single treatment arm, time from registration)

    All-cause mortality at 12 months

  7. Infection-related mortality at 12 months

    Time frame: 12 months following randomisation (or, in domains with a single treatment arm, time from registration)

    Infection-related mortality at 12 months

  8. Time free from hospitalisation with antimicrobial administration with therapeutic intent from randomisation to 12 months.

    Time frame: 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.

  9. Occurrence of one or more treatment-related adverse events

    Time frame: 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.

  10. Number of treatment-related adverse events.

    Time frame: 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.

  11. Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months

    Time frame: 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

  12. 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

    Time frame: 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

  13. Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the questionnaire.

    Time frame: 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.

  14. Costs associated with allocated treatment arm and infections during study.

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Monash University

Other

Registry information

Official study title

A Randomised Platform Trial Evaluating the Role of Interventions to Prevent Infection in Patients With Acquired Hypogammaglobulinemia Secondary to Haematological Malignancies - RATIONAL-PT (Core)

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Oct 1, 2025
Registry last updated
Oct 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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