Restrictive Versus Standard Antibiotic Treatment During CAR-T Therapy
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorZealand University Hospital
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
None
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
ceftazidime
DrugIntravenous 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
DrugOral 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
Other interventionParticipants 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.
Treatment groups
150 Participants
are divided into 2 treatment groupsGroup A: Restrictive Antibiotic StrategyExperimental treatment 2 interventions
Group B: Standard-of-Care Antibiotic StrategyActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
Gut Microbiota Alpha Diversity at Day 28
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.
Time frame
Day 28 after CAR-T-cell infusion (±3 working days)Secondary outcomes
1
Longitudinal Gut Microbiota Alpha Diversity
Gut microbiota alpha diversity measured by the Shannon diversity index in stool samples collected at randomization, around CAR-T-cell infusion, at day 28, and at the end-of-treatment evaluation. Longitudinal differences between treatment groups will be assessed across the protocol-defined sampling time points.
Time frame
From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion2
Gut Microbiota Beta Diversity
Differences in gut microbial community composition between treatment groups, assessed using beta-diversity metrics in stool samples collected at the protocol-defined sampling time points.
Time frame
From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion3
Relative Abundance of Predefined Beneficial Bacterial Taxa
Between-group differences and longitudinal changes in the relative abundance of predefined beneficial bacterial taxa in stool samples.
Time frame
From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion4
Infectious Complications
Number, type, and severity of infectious complications, including clinically documented infection, fever of unknown origin, bloodstream infection, sepsis, Clostridioides difficile infection, infection-related intensive care unit admission, and infection-related mortality. Events will be summarized separately for each predefined period.
Time frame
Randomization to CAR-T-cell infusion; day 0-28; and day 29-90 after infusionSponsors and contacts
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Source ClinicalTrials.gov
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