ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12624000961549

Ethics application status

Approved

Date submitted

5/07/2024

Date registered

8/08/2024

Date last updated

27/10/2024

Date data sharing statement initially provided

8/08/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

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

Scientific 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)

Secondary ID [1]

TRU-RPT-22

Universal Trial Number (UTN)

Trial acronym

RATIONAL-PT

Linked study record

ACTRN12624000964516: The 'Start-Ig' Domain of RATIONAL-PT.
ACTRN12624000963527: The 'Stop-Ig' Domain of RATIONAL-PT.
ACTRN12624000962538: The 'Dose-Ig' Domain of RATIONAL-PT.
ACTRN12616001723471: The RATIONAL Trial was a feasibility trial which is now completed and informed the development of the RATIONAL-PT, and in particular the Start-Ig domain.
ACTRN12622000359730: The RATIONALISE trial is an ongoing trial and related to the Stop-Ig domain.

Health condition

Health condition(s) or problem(s) studied:

haematological malignancy

hypogammaglobulinemia

Condition category

Condition code

Cancer

Myeloma

Cancer

Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Cancer

Leukaemia - Chronic leukaemia

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

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.

Initially the researchers will be investigating how safe and effective immunoglobulin replacement therapy is compared to oral antibiotics to prevent serious infections in patients with blood cancers, and also comparing different approaches to immunoglobulin dosing to determine the best dose of immunoglobulin for infection prevention. Further comparisons may be added to the platform.

Each comparison will be included as a sub-component, or ‘domain’, of the RATIONAL-PT. The treatments used in each domain may not be the same. Examples of treatments may include intravenous immunoglobulin, sub-cutaneous immunoglobulin and oral antibiotics. The duration of the trial-related treatment is 12 months in each domain.

Investigational products to be trialled will be considered and approved by the International Trial Steering Committee (ITSC). The ITSC will include members with experience and knowledge of the trial design, domain-specific expertise and regional-specific expertise.

Participants who have enrolled in and completed one domain may be invited to participate in another domain appropriate to their changed status. Each domain has its own domain-specific selection criteria, therefore eligibility for one domain does not imply eligibility for other domains.

The anticipated duration of the trial is 5 years. However, due to the adaptive platform design, trial duration may be extended in future with the addition of new domains.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Not applicable.

Control group

Uncontrolled

Outcomes

Primary outcome [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.

Timepoint [1]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [1]

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

Timepoint [1]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [2]

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

Timepoint [2]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [3]

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

Timepoint [3]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [4]

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

Timepoint [4]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [5]

Number of microbiologically documented infections from randomisation to 12 months.

Timepoint [5]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [6]

All-cause mortality at 12 months

Timepoint [6]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [7]

Infection-related mortality at 12 months

Timepoint [7]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [8]

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

Timepoint [8]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [9]

Occurrence of one or more treatment-related adverse events

Timepoint [9]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [10]

Number of treatment-related adverse events.

Timepoint [10]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [11]

Isolation of fluoroquinolone resistant organisms, co-trimoxazole resistant organisms, extended spectrum beta lactamases or multidrug resistant organisms from randomisation to 12 months.
This will be assessed as a composite outcome.

Timepoint [11]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [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.
This will be assessed as a composite outcome.

Timepoint [12]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Secondary outcome [13]

Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the EQ-5D-5L questionnaire.

Timepoint [13]

Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation

Secondary outcome [14]

Quality of Life (QoL) measured at randomisation then 3, 6, 9 and 12 months, using the EORTC QLQ-C30 questionnaire.

Timepoint [14]

Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation

Secondary outcome [15]

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

Timepoint [15]

Prior to randomisation in each domain, then at Month 3, Month 6, Month 9 and Month 12 post-randomisation.

Secondary outcome [16]

Costs associated with allocated treatment arm and infections during study. This will be assessed as a composite outcome.

Timepoint [16]

12 months following randomisation in each domain (or, in domains with a single treatment arm, time from registration)

Eligibility

Key inclusion criteria

1. Aged greater than or equal to 18 years of age
2. Diagnosis of haematological malignancy, including CLL, MM or NHL
3. 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)
4. Life expectancy > 12 months
5. Able to give informed consent

Additional eligibility criteria will apply for each domain of the RATIONAL Platform Trial.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

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

Additional eligibility criteria will apply for each domain of the RATIONAL Platform Trial.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

The RATIONAL Platform Trial (RATIONAL-PT) provides the framework on which different interventions and domains exist within the trial. The domains linked to the platform detail the specific interventions to be studied within that domain and whether or not randomisation will be used for treatment allocation.

Phase

Phase 2 / Phase 3

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Up to 900 participants will be recruited to the RATIONAL-PT, including up to 300 per domain. The aim of the platform is to determine optimal supportive care interventions for patients with haematological malignancies. The primary outcome for the platform is 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. Data from each domain will contribute to the primary analysis.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/11/2024

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

900

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

ACT,NSW,SA,VIC

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Country [1]

Australia

Funding source category [2]

Government body

Name [2]

Australian Department of Health and Aged Care, Medical Research Future Fund (MRFF)

Address [2]

Country [2]

Australia

Primary sponsor type

University

Name

Monash University

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Other Collaborative groups

Name [1]

Australasian Leukaemia & Lymphoma Group (ALLG)

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

https://www.alfredhealth.org.au/research/ethics-research-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

13/11/2023

Approval date [1]

04/01/2024

Ethics approval number [1]

HREC/103986/Alfred-2023 (Local Reference: Project 726/23)

Summary

Brief summary

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. 

Who is it for?
Patients with  a blood cancer and low levels of certain antibodies (immunoglobulins) in the blood.
Your treating doctor will check your eligibility to participate in this study. You will need to undergo screening assessments to find out if it is safe for you to be involved in the study.

Study details:
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. Depending on the domain you are participating in, you may be assigned to a study treatment by chance (randomly). Following randomisation (if applicable), you will be asked to complete your Day 1 assessments. 

If eligible to participate in a domain of the RATIONAL-PT, your active study participation in that domain will last for 13 months and all participants will return to the hospital for a study visit every 3 months (4 more in-person visits after Day 1). During each month of the 12-month treatment period except the months in which you are attending in-person study visits, you will receive a phone call from your treating clinical team to check your progress (8 calls in total).

Even if you are recommended to, or choose to, stop your domain treatment during the 12-month treatment period, you will be asked to continue attending study visits and having phone calls until the end of the trial period (13 months in total) because we are still interested in your outcomes.

At the end of your participation on the study, your doctor will decide if you still require treatment to prevent infection, and if you do, whether to continue on the treatment you received during the study (immunoglobulins, antibiotics or none).

The results of this trial will inform clinical decision making about the use of immunoglobulin and oral antibiotics for patients with blood cancers. Your participation may help doctors who treat patients with blood diseases in the future to know which treatment to prescribe to try to prevent serious infections.

Trial website

Trial related presentations / publications

Public notes

The RATIONAL-PT trial includes the following optional sub-studies:

 - Qualitative Sub-Study: The purpose of this sub-study is to explore your experiences of immunoglobulins, antibiotics and other treatments that affect infection risk. If you agree to take part, you will be asked to participate in a one-to-one interview. Your responses and views will help us build a more complete picture of preferences of treatments used to reduce infection from a patient's perspective.

 - Pharmacokinetic/Pharmacodynamic (PK/PD) Sub-Study: The purpose of this sub-study is to better understand what dose of immunoglobulin is likely to provide the greatest benefit to patients. This sub-study will require additional blood samples which will be drawn at various timepoints around a single dose of immunoglobulin. By measuring the amount of immunoglobulin in your blood at different timepoints, it will help to determine how long it takes for immunoglobulin to be absorbed into your body, how long it stays in the body after it has been absorbed, and the relationship between the amount in the body and its effect on the body.

 - Patient Preferences Sub-study: The purpose of this sub-study is to explore your preferences for treatments that affect infection risk. If you agree to participate you will be asked to complete an online survey. During the survey we will ask you to imagine making choices between different treatment options for preventing infection based on different aspects of the treatment (for example, how often it is administered, how long it takes to administer, the likelihood of side effects, risk of infection and out-of-pocket costs and so on).

RATIONAL-PT participants may be invited to participate in one or more of the above sub-studies. Participation is optional and participants may still participate in RATIONAL-PT even if they choose not to participate in any or all of the sub-studies.

Contacts

Principal investigator

Name

Prof Zoe McQuilten

Address

Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004

Country

Australia

Phone

+61 3 9903 0379

Fax

zoe.mcquilten@monash.edu

Contact person for public queries

Name

Zoe McQuilten

Address

Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004

Country

Australia

Phone

+61 3 9903 0379

Fax

zoe.mcquilten@monash.edu

Contact person for scientific queries

Name

Zoe McQuilten

Address

Transfusion Research Unit, Public Health and Preventive Medicine, Monash University, Level 1, 553 St Kilda Road, Melbourne, VIC 3004

Country

Australia

Phone

+61 3 9903 0379

Fax

zoe.mcquilten@monash.edu

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Individual participant data will not be publicly available. Data will only be presented as a whole, no individual data will be published or presented.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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