Methylene blue added to treat CAR‑T–related CRS and ICANS

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

This study will test whether giving methylene blue alongside standard care helps people who develop CRS or ICANS after CAR‑T cell or bispecific antibody therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, immunotherapy, tocilizumab, cetuximab, ruxolitinib
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07169487 on ClinicalTrials.gov

What this trial studies

This is a Phase I, prospective, single‑arm 3+3 dose‑escalation trial testing adjunctive intravenous methylene blue in patients who develop ASTCT grade ≥1 CRS or ICANS after CAR‑T or bispecific antibody therapy. Participants will be enrolled into three escalating dosing cohorts (1, 2, and 3 mg/kg IV once daily) with treatment given for 3–5 consecutive days and close monitoring of vital signs, laboratory inflammatory markers, and neurological status. Dosing decisions will follow standard 3+3 safety rules and concomitant standard supportive treatments (eg, tocilizumab, steroids) are permitted. The trial builds on preclinical data suggesting methylene blue can reduce CRS/ICANS signs and protect neurovascular integrity without impairing T‑cell antitumor activity.

Who should consider this trial

Good fit: Adults (≥18) with hematologic malignancies who received CAR‑T cells or bispecific antibodies and then develop ASTCT grade ≥1 CRS or ICANS, with LVEF >45%, estimated life expectancy ≥3 months, and no contraindications to methylene blue (eg, G6PD deficiency).

Not a fit: Patients with G6PD deficiency, known methylene blue allergy, pregnancy or breastfeeding, significant uncontrolled cardiac conduction disease, or other listed exclusions (including HIV seropositivity where disallowed) are not eligible and would not receive benefit from this protocol.

Why it matters

Potential benefit: If successful, methylene blue could reduce the severity or duration of immunotherapy‑related CRS and ICANS while preserving antitumor immune function.

How similar studies have performed: Preclinical studies report benefit for methylene blue in models of CRS/ICANS, but clinical evidence is very limited and this Phase I study represents one of the first clinical tests for this indication.

Eligibility criteria

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jianxiang Wang — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Jianxiang Wang

Conditions Cytokine Release Syndrome; ICANS; Methylene Blue; Immune Effector Cell-Associated Neurotoxicity Syndrome; CAR-T Cell Therapy; Immunotherapy-Related Toxicity