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

NCT07202052 | Recruiting Phase 2 DMC

• 1 other identifier: TRU-RPT-22
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Myeloma; Non-Hodgkin's Lymphoma; Leukemia

Keywords

immunoglobulin; antibiotics; myeloma; leukaemia; lymphoma; non Hodgkins; infection; infections; blood; cancer; haematology

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (14)

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

  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.

  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.

  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.

  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.

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

Study Arms (3)

Start Immunoglobulin

OTHER

Patients eligible to start immunoglobulin are randomly assigned to: * receive either prophylactic antibiotic * or Ig replacement.

Biological: Intravenous immunoglobulin; Drug: Trimethoprim / Sulfamethoxazole

Stop Immunoglobulin

OTHER

Patients eligible to stop immunoglobulin are randomly assigned to: * Stop Ig and take daily antibiotics * Stop Ig and take antibiotics only when infections occur * Continue Ig therapy

Biological: Intravenous immunoglobulin; Drug: Trimethoprim / Sulfamethoxazole; Drug: Amoxicillin clavulanic acid

Dose Immunoglobulin

OTHER

Patients receiving IVIg are randomly assigned to: * Continue with standard dose (0.4 g/kg) * Switch to a lower dose (0.25 g/kg)

Biological: Intravenous immunoglobulin (IVIG)

Interventions

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.

Also known as: Subcutaneous immunoglobulin

Start Immunoglobulin; Stop 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.

Also known as: co-trimoxazole

Start Immunoglobulin; Stop Immunoglobulin

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.

Also known as: Ciprofloxacin

Stop Immunoglobulin

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.

Dose Immunoglobulin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Monash University: lead

Study Sites (3)

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Austin Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Northern Health

Melbourne, Victoria, 3004, Australia

RECRUITING

Related Links

• Study Website

MeSH Terms

Conditions

Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin; Leukemia; Lymphoma; Infections; Neoplasms

Interventions

Immunoglobulins, Intravenous; Trimethoprim, Sulfamethoxazole Drug Combination; Amoxicillin-Potassium Clavulanate Combination; Ciprofloxacin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Officials

• Zoe McQuilten, Professor

  Monash University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: An independent outcome adjudication committee will meet to review and adjudicate infection outcome data. These committee members will be blinded to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: October 1, 2025
• Study Start: May 6, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)