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RecruitingLast updated: 23 October 2025

RATIONAL-PT (Start-Ig Domain): A trial for people with blood cancers who are eligible to receive or are currently receiving immunoglobulin replacement to prevent infectionA randomised platform trial evaluating the role of interventions to prevent infection in patients with acquired hypogammaglobulinemia secondary to haematological malignancies

Trial purpose

Medical clipboardSide effect and wellbeing

Tumor type

Blood Cancers Haematological

Age

People18+

Trial acronym

RATIONAL-PT (Start-Ig Domain)

Clinical summary

Summary

This research project forms part of the RATIONAL Platform Trial. 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 people with blood cancers.

While immunoglobulin is commonly used long-term in people with blood cancer, we don't know whether oral antibiotics are just as good at preventing serious infections. The research project is investigating the use of oral antibiotics (in tablet form) to determine if they are as effective as immunoglobulin (either IVIg or SCIg) in reducing the risk of infections in people with blood cancers.

You may be eligible if you have a blood cancer and low levels of certain antibodies (immunoglobulins) in the blood. Your treating doctor will check to find out if you're eligible to participate, and you will need to undergo screening assessments to see if it's safe for you to be involved.

Study details

In this clinical trial domain, participants will be divided into two groups (arms) to compare the different treatments. There is one usual care group and one investigational group. Each participant is put into a group by chance (randomly). The two groups are:

  • Start immunoglobulin (IVIg or SCIg) replacement therapy.
  • Start oral antibiotics to take every day.

If you are 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 phon ecall 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 researchers are still interested in your outcomes.

At the end of your participation in 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 people with blood cancers. Your participation may help doctors who treat people with blood diseases in future to know whether to prescribe oral antibiotics or immunoglobulins to try to prevent the onset of serious infections. 

Conditions

This trial is treating people with a haematological malignancy, including chronic lymphocytic leukaemia (CLL), multiple myeloma (MM), or non-Hodgkin's lymphoma (NHL) and are eligible to receive immunoglobulin replacement

Eligibility

Inclusion

Patients are eligible for the Start-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Start-Ig domain.

RATIONAL-PT inclusion criteria:
1. Aged greater than or equal to 18 years of age
2. Diagnosis of haematological malignancy, including Chronic Lymphocytic Leukaemia (CLL), Multiple Myeloma (MM) or Non-Hodgkin's Lymphoma (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

Start-Ig domain inclusion criteria:
None.

Exclusion

Patients are eligible for the Start-Ig domain of the RATIONAL-PT if they fulfil eligibility for both RATIONAL-PT and the Start-Ig domain.

RATIONAL-PT exclusion criteria:
1. Treating team deems enrolment in the study is not in the best interests of the patient

Start-Ig domain exclusion criteria:
1. Prior or planned allogeneic haematopoietic stem cell transplantation.
2. Already receiving systemic antibiotic prophylaxis for the purpose of preventing bacterial infection (NB: patients may receive antiviral, antifungal and Pneumocystis jirovecii Pneumonia (PJP) prophylaxis).
3. Received immunoglobulin replacement in the preceding three months.
4. Objection to receiving immunoglobulin products.
5. Known history of IgA deficiency with anti-IgA.
6. History of severe allergy to immunoglobulin products.
7. Current active infection requiring systemic antibiotics.
8. Allergy or intolerance of all domain antibiotic options.
9. Pregnant or breastfeeding.
10. Severe renal impairment (estimated or measured creatinine clearance of < 30 mL/min).
11. Previous splenectomy.
12. Previous participation in this domain.
13. Treating team deems enrolment in the domain is not in the best interest of the patient.

Inclusion

  • You are able to swallow medication by mouth.
  • You have the type of cancer, symptoms, or health risks that this clinical trial is focused on.

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

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More information

Trial Identifiers

Information on this page is partially produced from ANZCTR, ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Australasian Leukaemia & Lymphoma Group (ALLG)

Scientific Title

A randomised platform trial evaluating the role of interventions to prevent infection in patients with acquired hypogammaglobulinemia secondary to haematological malignancies

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