Restrictive Versus Standard Antibiotic Treatment During CAR-T Therapy

NCT07842198 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: CARMicBK26-02535
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Large B-Cell Lymphoma (LBCL); Multiple Myeloma (MM); Gut Microbiota

Keywords

CAR-T-cell therapy; Antibiotic strategy; Microbiome-sparing antibiotics; Ceftazidime; Ciprofloxacin; Gut microbiome; Febrile neutropenia; Shannon diversity index; Metabolomics

Outcome Measures

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.

  Day 28 after CAR-T-cell infusion (±3 working days)

Secondary Outcomes (18)

• Longitudinal Gut Microbiota Alpha Diversity

  From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion

• Gut Microbiota Beta Diversity

  From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion

• Relative Abundance of Predefined Beneficial Bacterial Taxa

  From randomization through the end-of-treatment evaluation, approximately 3-6 months after CAR-T-cell infusion

• Infectious Complications

  Randomization to CAR-T-cell infusion; day 0-28; and day 29-90 after infusion

• Total Systemic Antibacterial Exposure

  From randomization through day 28 after CAR-T-cell infusion

Study Arms (2)

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.

Drug: ceftazidime; Drug: ciprofloxacin

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.

Other: Standard-of-Care Antibiotic Strategy

Interventions

ceftazidime DRUG

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.

Restrictive Antibiotic Strategy

ciprofloxacin DRUG

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.

Restrictive Antibiotic Strategy

Standard-of-Care Antibiotic Strategy OTHER

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.

Standard-of-Care Antibiotic Strategy

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zealand University Hospital: lead

Study Sites (1)

Zealand University Hospital

Roskilde, Vælg Venligst Region, 4000, Denmark

Location

MeSH Terms

Conditions

Multiple Myeloma; Febrile Neutropenia

Interventions

Ceftazidime; Ciprofloxacin

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Cephaloridine; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Central Study Contacts

Lars M Pedersen, MD

CONTACT

+45 47324803; lmpn@regionsjaelland.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized 1:1 to two parallel treatment groups and stratified by disease cohort: large B-cell lymphoma or multiple myeloma.

Study Record Dates

• First Submitted: September 20, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: September 25, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)