Restrictive Versus Standard Antibiotic Treatment During CAR-T Therapy

Condition(s) studied

Investigational drug(s) / intervention(s)

ceftazidime: Intravenous ceftazidime will be used as initial empirical antibacterial treatment when clinically indicated during the period from randomization through day 28 after CAR-T-cell infusion. Dosing and renal dose adjustment will follow the applicable product information and local clinical practice. Treatment may be modified or broadened at any time when clinically required.

ciprofloxacin: Oral ciprofloxacin may be used as protocol-defined step-down therapy after adequate infection control and clinical stabilization or as antibacterial prophylaxis when clinically indicated in the absence of suspected ongoing infection. Ciprofloxacin will not be used as initial empirical monotherapy for suspected infection. Dosing and renal dose adjustment will follow the applicable product information and local clinical practice.

Standard-of-Care Antibiotic Strategy: Participants will receive antibacterial prophylaxis and treatment according to unrestricted local standard-of-care practice. Selection, dosing, modification, escalation, and duration of antibacterial treatment will be determined by the treating physician according to clinical findings, microbiological results, and local guidelines.

Study summary

The purpose of the CARMic study is to investigate whether a restrictive, microbiome-sparing antibiotic strategy can better preserve the gut microbiota in patients undergoing chimeric antigen receptor T-cell (CAR-T) therapy without compromising infectious safety.

This is a randomized, open-label Phase II trial enrolling 150 adults with large B-cell lymphoma or multiple myeloma who are scheduled to receive standard-of-care CAR-T therapy. Participants will be randomly assigned in a 1:1 ratio to either a restrictive antibiotic strategy based on ceftazidime and/or ciprofloxacin or an unrestricted standard-of-care antibiotic strategy. The assigned strategy will apply from randomization until 28 days after CAR-T-cell infusion. Antibiotic treatment may be modified or broadened at any time when clinically indicated.

The primary question is whether the restrictive antibiotic strategy results in greater gut microbial diversity 28 days after CAR-T-cell infusion compared with standard-of-care antibiotic treatment. Gut microbial diversity will be assessed in stool samples using the Shannon diversity index.

The study will also compare infections, antibiotic exposure, adherence to the assigned strategy, CAR-T-related toxicities, treatment response, relapse, progression-free survival, and overall survival between the two groups. Changes in gut microbiota composition and in blood and stool metabolomic and proteomic profiles will be evaluated over time. Blood and stool samples will be collected at randomization, around the time of CAR-T-cell infusion, 28 days after infusion, and at the end-of-treatment evaluation approximately 3-6 months after infusion.

Eligibility

Primary outcome measure(s)

• Gut Microbiota Alpha Diversity at Day 28 — Day 28 after CAR-T-cell infusion (±3 working days)
  Gut microbiota alpha diversity measured by the Shannon diversity index in a stool sample collected at day 28 after CAR-T-cell infusion. The Shannon index quantifies within-sample microbial diversity by incorporating both microbial richness and evenness. The treatment effect will be expressed as the adjusted mean difference in the Shannon diversity index between the restrictive antibiotic strategy and the standard-of-care antibiotic strategy, calculated as restrictive strategy minus standard of care. A positive difference favors the restrictive strategy.

Trial sites (1)

More Zealand University Hospital trials in Denmark

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