RecruitingPhase 2Phase 3NCT07202052

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

A Randomised Platform Trial Evaluating the Role of Interventions to Prevent Infection in Patients With Acquired Hypogammaglobulinemia Secondary to Haematological Malignancies - RATIONAL-PT (Core)


Sponsor

Monash University

Enrollment

900 participants

Start Date

May 6, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • 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

Exclusion Criteria1

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

Interventions

BIOLOGICALIntravenous immunoglobulin

(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.

DRUGTrimethoprim / Sulfamethoxazole

Once daily trimethoprim-sulfamethoxazole (co-trimoxazole) 160mg/800mg. Doxycycline 100mg daily as an alternative for patients with hypersensitivity to co-trimoxazole.

DRUGAmoxicillin clavulanic acid

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.

BIOLOGICALIntravenous immunoglobulin (IVIG)

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.


Locations(3)

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Austin Hospital

Melbourne, Victoria, Australia

Northern Health

Melbourne, Victoria, Australia

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NCT07202052


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