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NCT Number: NCT05678621

Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension

The aim of the study is to find out if patients with blood cancers receiving immunoglobulin (Ig) for the purpose of preventing infections can safety stop immunoglobulin after six months of therapy, and take oral antibiotics instead to prevent serious infections.

Patients may be eligible to join this study if they are aged 18 years or above, have an acquired hypogammaglobulinaemia secondary to a haematological malignancy, and have been receiving intravenous or subcutaneous Ig for longer than 6 consecutive months.

Participants will be randomised (allocated by chance) to one of three treatment groups, as follows:

* Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to take every day (ARM A) * Stop immunoglobulin (IVIg or SCIg) and be given oral antibiotics to keep at home to use as soon as symptoms of an infection develop (ARM B) * Continue receiving immunoglobulin (IVIg or SCIg) - this is the usual care group (ARM C)

The duration of each treatment is for 12 months from study entry.

Participants will be asked to attend a screening/baseline visit so that their treating clinician can assess their eligibility for the trial and collect baseline data. If eligible for the trial, participants will then be randomly allocated to one of the three treatment groups.

Once randomised, active participation in the study will last for 13 months. During this period, participants will be asked to return to the hospital for a study visit every 3 months, with monthly telephone visits to check-in on your progress between each in-person visit. Participants will also be asked to complete a study diary, recording treatment compliance and signs/symptoms of infection experienced throughout the study period.

Types of assessments and data collected will include: Medical history, demographics, physical examination, blood tests, stool sample, quality of life questionnaires, information about your general health, hospitalisations, medications and procedures. In order to assess and compare the cost-effectiveness of the treatment groups, the study team will also request authorisation from participants to access their Medicare Benefits Schedule (MBS), Pharmaceutical Benefits Scheme (PBS), and Australian Immunisation Register (AIR) data.

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Key information

Conditions

Haematological Malignancy Agammaglobulinemia Blood Protein Disorders Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Hypogammaglobulinemia Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Infections Leukemia Lymphatic Diseases Lymphoma Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Canberra Hospital, Garran, Australian Capital Territory, Australia

Loading trial locations.

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 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.

Treatment and study plan

trimethoprim-sulfamethoxazole (co-trimoxazole)

Drug

Doxycycline is an alternative for participants with hypersensitivity to co-trimoxazole.

amoxycillin/clavulanic acid and ciprofloxacin

Drug

clindamycin is an alternative to amoxycillin/clavulanic acid for participants with hypersensitivity to penicillin.

immunoglobulins

Drug

Intravenous monthly immunoglobulin or subcutaneous weekly immunoglobulin

Primary outcomes

  1. Event-free survival (EFS), defined as time from randomisation 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

Secondary outcomes

  1. Proportion of patients who develop at least 1 Grade 3 or higher infection(s) from randomisation to 12 months.

    Time frame: 12 months following randomisation

  2. Proportion of patients with one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months.

    Time frame: 12 months following randomisation

  3. Number of clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months. Data collected from medical records will inform this outcome measure.

    Time frame: 12 months following randomisation

  4. Proportion of patients with one or more microbiologically documented bacterial infections.

    Time frame: 12 months following randomisation

  5. Number of microbiologically documented bacterial infections.

    Time frame: 12 months following randomisation

  6. Time free from hospitalisation and antimicrobials with therapeutic intent.

    Time frame: 12 months following randomisation

  7. Proportion of patients with one or more treatment-related adverse events

    Time frame: 12 months following randomisation

  8. Number of treatment-related adverse events.

    Time frame: 12 months following randomisation

  9. Proportion of patients with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated.

    Time frame: 12 months following randomisation

  10. Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated.

    Time frame: 12 months following randomisation

  11. Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months

    Time frame: Randomisation and 3, 6, 9 and 12 months following randomisation.

    QoL will be assessed using the EORTC QLQ-C30 questionnaire.

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

    Time frame: Randomisation and 3, 6, 9 and 12 months following randomisation.

    QoL will be assessed using the Functional Assessment of Cancer Therapy - Neutropenia (FACT-N) questionnaire.

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

    Time frame: Randomisation and 3, 6, 9 and 12 months following randomisation.

    QoL will be assessed using the EQ-5D-5L questionnaire.

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

    Time frame: 12 months following randomisation

    Costs associated with each treatment arm with be aggregated into Australian dollars. Aggregate costs will be calculated based on the following data sources: medical records, infection-related hospitalisations (using unit costs based on unlinked data from the Victorian Admitted Episodes Dataset, Victorian Emergency Minimum Dataset and the Victorian Cost Data Collection), Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Immunisation Registry (AIR) data.

  15. Cost effectiveness of the allocated treatment arm

    Time frame: 12 months following randomisation

    Differences in costs and Quality Adjusted Life Years (QALYs) for each of the treatment arms will be aggregated into a cost effectiveness ratio. The following data sources will be used to calculate this outcome measure: the EORTC QLQ-C30 questionnaire will be used to calculate QALYS. Costs will be calculated based on the following data sources: medical records, infection-related hospitalisations (using unit costs based on unlinked data from the Victorian Admitted Episodes Dataset, Victorian Emergency Minimum Dataset and the Victorian Cost Data Collection), Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS) and Australian Immunisation Registry (AIR) data.

  16. Trough IgG level at 3, 6, 9 and 12 months from baseline.

    Time frame: 3, 6, 9 and 12 months from baseline

  17. Proportion of patients in immunoglobulin cessation treatment arms who restart Ig over 12 months.

    Time frame: 12 months following randomisation

  18. Covid anti-spike protein levels at baseline, 3, 6, 9, and 12 months.

    Time frame: 3, 6, 9 and 12 months following baseline

Study contacts

Contact information is provided by the study sponsor or research team.

Prof Zoe McQuilten

CONTACT

[email protected]

+61 3 9903 0379

Sponsors and collaborators

Lead sponsor

Monash University

Other

Registry information

Official study title

A Randomised Controlled Trial of Continuing Immunoglobulin Therapy, or Stopping With or Without Prophylactic Antibiotics, on Infection Rate in Patients With Acquired Hypogammaglobulinemia Secondary to Haematological Malignancies.

Acronym: RATIONALISE

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Jan 10, 2023
Registry last updated
Apr 19, 2024

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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