Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study
Exploration of Efficacy and Safety of Adjunctive Methylene Blue in the Treatment of Immunotherapy-related CRS and ICANS: A Prospective, Single-arm, Phase I Clinical Study
Institute of Hematology & Blood Diseases Hospital, China
18 participants
Jun 28, 2025
INTERVENTIONAL
Conditions
Summary
This Phase I, prospective, single-arm clinical study aims to evaluate the efficacy and safety of adjunctive methylene blue (MB) in patients experiencing cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) following CAR-T cell therapy or bispecific antibody treatment. Preclinical studies demonstrated that MB alleviates CRS/ICANS-related symptoms, preserves the antitumor function of T cells, and modulates neuroinflammation without compromising immune efficacy. The study will employ a 3+3 dose-escalation design with three MB dosing cohorts, with treatment administered intravenously for 3-5 consecutive days. Vital signs, laboratory markers, and neurological status will be closely monitored, and concomitant standard supportive therapies will be permitted.
Eligibility
Inclusion Criteria6
- Diagnosed with hematologic malignancies based on cytomorphology and immunophenotyping; age ≥18 years.
- Received immunotherapy (e.g., CAR-T cells, bispecific antibodies) and developed CRS or ICANS of ASTCT Grade ≥1.
- Estimated life expectancy ≥3 months.
- Male and female participants of childbearing potential agree to use effective contraception.
- Left ventricular ejection fraction (LVEF) >45% by echocardiography.
- Ability to understand and sign informed consent and willingness to comply with study requirements.
Exclusion Criteria7
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
- Known allergy to methylene blue.
- Pregnant or breastfeeding women.
- Known HIV seropositivity. HIV testing may be required according to local laws or regulations.
- History of clinically significant ventricular arrhythmia, unexplained syncope (not vasovagal), sinoatrial block, or higher-degree atrioventricular (AV) block with chronic bradycardia (unless a permanent pacemaker is implanted).
- Psychiatric disorders that may interfere with completion of treatment or informed consent.
- Any other condition deemed unsuitable for participation by the investigator.
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Interventions
Intravenous infusion of methylene blue once daily for 3-5 consecutive days at doses of 1 mg/kg, 2 mg/kg, or 3 mg/kg, administered over 20 minutes, following CAR-T or bispecific antibody infusion in patients who develop Grade ≥1 CRS or ICANS.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07169487