Clinical trial NCT05678621: Role of Antibiotic Therapy or Immunoglobulin On iNfections in hAematoLogy: Immunoglobulin Stopping or Extension
Official 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Haematological Malignancy
Hypogammaglobulinemia
Keywords: Myeloma
Lymphoma
Leukaemia
Blood cancer
Malignancy
Infection
Antibiotic
Anti-infective agent
Immunoglobulin
Lead sponsor: Monash University
Sponsor class: OTHER
First posted: 2023-01-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Aged greater than or equal to 18 years of age
2. Diagnosis of chronic lymphocytic leukaemia (CLL), multiple myeloma (MM) or non-Hodgkin lymphoma (NHL).
3. Patients must be receiving Ig (IV or subcutaneous - SCIg) replacement for prevention of bacterial infections due to hypogammaglobulinaemia for longer than 6 consecutive months.
4. Patient is eligible for trial of Ig cessation in the opinion of the treating clinician and local investigator.
5. Life expectancy greater than 12 months.
6. Able to give informed consent, and willing and able to comply with each of the treatment arms.

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 antimicrobial treatment.
3. Already receiving daily antibiotic prophylaxis for the purpose of preventing bacterial infection (Note: 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 that are likely to limit 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 less than 30 mL/min).
8. Previous splenectomy.
9. Previous participation in this trial.
10. Treating team deems enrolment in the study is not in the best interests of the patient.

Primary outcomes:
measure: 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.
timeFrame: 12 months following randomisation
Secondary outcomes:
measure: Proportion of patients who develop at least 1 Grade 3 or higher infection(s) from randomisation to 12 months.
timeFrame: 12 months following randomisation
measure: Proportion of patients with one or more clinically documented infections (symptoms/signs of infection requiring antimicrobial treatment) to 12 months.
timeFrame: 12 months following randomisation
measure: 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.
timeFrame: 12 months following randomisation
measure: Proportion of patients with one or more microbiologically documented bacterial infections.
timeFrame: 12 months following randomisation
measure: Number of microbiologically documented bacterial infections.
timeFrame: 12 months following randomisation
measure: Time free from hospitalisation and antimicrobials with therapeutic intent.
timeFrame: 12 months following randomisation
measure: Proportion of patients with one or more treatment-related adverse events
timeFrame: 12 months following randomisation
measure: Number of treatment-related adverse events.
timeFrame: 12 months following randomisation
measure: Proportion of patients with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated.
timeFrame: 12 months following randomisation
measure: Number of infections with fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms isolated.
timeFrame: 12 months following randomisation
measure: Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months
timeFrame: Randomisation and 3, 6, 9 and 12 months following randomisation.
measure: Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months
timeFrame: Randomisation and 3, 6, 9 and 12 months following randomisation.
measure: Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months
timeFrame: Randomisation and 3, 6, 9 and 12 months following randomisation.
measure: Costs associated with allocated treatment arm and infections during study
timeFrame: 12 months following randomisation
measure: Cost effectiveness of the allocated treatment arm
timeFrame: 12 months following randomisation
measure: Trough IgG level at 3, 6, 9 and 12 months from baseline.
timeFrame: 3, 6, 9 and 12 months from baseline
measure: Proportion of patients in immunoglobulin cessation treatment arms who restart Ig over 12 months.
timeFrame: 12 months following randomisation
measure: Covid anti-spike protein levels at baseline, 3, 6, 9, and 12 months.
timeFrame: 3, 6, 9 and 12 months following baseline
Other outcomes:
Locations:
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
Study officials:
affiliation: Monash University
name: Prof Erica Wood
role: PRINCIPAL_INVESTIGATOR
affiliation: Monash University
name: Prof Zoe McQuilten
role: PRINCIPAL_INVESTIGATOR
References: