CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Age 18 years or older. Relapsed or refractory large B-cell lymphoma according to the current World Health Organization classification, or relapsed or refractory multiple myeloma according to the current International Myeloma Working Group classification.

Eligible for treatment with a CAR-T-cell product authorized in the European Union and recommended for reimbursement by the Danish Medicines Council.

A clinical decision to proceed with CAR-T-cell therapy has been made jointly by the participant and the treating physician.

Written informed consent to participate in the trial.

Exclusion Criteria:

Pregnancy or breastfeeding. Psychiatric illness or other condition that may interfere with the ability to understand or comply with the trial requirements.

Clinical signs of an uncontrolled serious infection. Severe colitis. Previous allergic reaction to cephalosporins or ciprofloxacin. Participants with a known allergy to other beta-lactam antibiotics, including penicillins, may be enrolled provided that they do not have a known allergy to cephalosporins.

主要终点：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. · Day 28 after CAR-T-cell infusion (±3 working days)
次要终点：Longitudinal Gut Microbiota Alpha Diversity；Gut Microbiota Beta Diversity；Relative Abundance of Predefined Beneficial Bacterial Taxa；Infectious Complications；Total Systemic Antibacterial Exposure；Exposure to Broad-Spectrum Antibiotics With Extended Anaerobic Coverage；Cytokine Release Syndrome；Immune Effector Cell-Associated Neurotoxicity Syndrome

• Restrictive Antibiotic Strategy · EXPERIMENTAL · Participants will follow a protocol-defined restrictive antibacterial strategy from randomization until day 28 after CAR-T-cell infusion. Intravenous ceftazidime will be used as initial empirical antibacterial treatment when clinically indicated. Oral ciprofloxacin may be used as step-down therapy following adequate infection control and clinical stabilization or as antibacterial prophylaxis when clinically indicated in the absence of suspected ongoing infection. Antibacterial treatment may be modified or broadened at any time when clinically required.
• Standard-of-Care Antibiotic Strategy · ACTIVE_COMPARATOR · Participants will receive antibacterial prophylaxis and treatment according to unrestricted local standard-of-care practice from randomization until day 28 after CAR-T-cell infusion. Selection, modification, escalation, and duration of antibacterial treatment will be determined by the treating physician according to clinical findings, microbiological results, and local guidelines.

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.