Methylene Blue: 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.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Diagnosed with hematologic malignancies based on cytomorphology and immunophenotyping; age ≥18 years.
2. Received immunotherapy (e.g., CAR-T cells, bispecific antibodies) and developed CRS or ICANS of ASTCT Grade ≥1.
3. Estimated life expectancy ≥3 months.
4. Male and female participants of childbearing potential agree to use effective contraception.
5. Left ventricular ejection fraction (LVEF) \>45% by echocardiography.
6. Ability to understand and sign informed consent and willingness to comply with study requirements.
Exclusion Criteria:
1. Glucose-6-phosphate dehydrogenase (G6PD) deficiency.
2. Known allergy to methylene blue.
3. Pregnant or breastfeeding women.
4. Known HIV seropositivity. HIV testing may be required according to local laws or regulations.
5. 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).
6. Psychiatric disorders that may interfere with completion of treatment or informed consent.
7. Any other condition deemed unsuitable for participation by the investigator.
Primary outcome measure(s)
Incidence and type of methylene blue-related serious adverse events (SAEs) — Up to Day 35 after initiation of methylene blue treatment The proportion of participants who experience methylene blue-related serious adverse events (SAEs), categorized by type, assessed according to NCI CTCAE v5.0 criteria. SAEs will be judged by the investigator to be related to methylene blue administration.
Impact of Methylene Blue on CAR-T/T Cell Expansion in Peripheral Blood — Up to Day 35 after initiation of methylene blue treatment Evaluation of CAR-T or T cell expansion in peripheral blood following methylene blue treatment, assessed by flow cytometry.
Impact of Methylene Blue on CAR-T/T Cell Therapy Efficacy — Baseline to Day 35 post-treatment initiation Proportion of participants achieving complete remission (CR), partial remission (PR), stable disease (SD), or experiencing relapse/progression, assessed according to immunotherapy response criteria (see Study Protocol for full criteria).
Trial sites (1)
Facility
City
Region
Status
Institute of Hematology & Blood Diseases Hospital
Tianjin
Tianjin Municipality
Recruiting
More Institute of Hematology & Blood Diseases Hospital, China trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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