Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study

NCT07169487 | Recruiting Phase 1

• 1 other identifier: IIT2025072
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cytokine Release Syndrome; ICANS

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Incidence and type of methylene blue-related serious adverse events (SAEs)

  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.

  Up to Day 35 after initiation of methylene blue treatment

• Impact of Methylene Blue on CAR-T/T Cell Expansion in Peripheral Blood

  Evaluation of CAR-T or T cell expansion in peripheral blood following methylene blue treatment, assessed by flow cytometry.

  Up to Day 35 after initiation of methylene blue treatment

• Impact of Methylene Blue on CAR-T/T Cell Therapy Efficacy

  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).

  Baseline to Day 35 post-treatment initiation

Secondary Outcomes (5)

• Incidence of Grade ≥3 CRS and ICANS

  Up to Day 35 after initiation of methylene blue treatment

• Duration of CRS and ICANS

  Up to Day 35 after initiation of methylene blue treatment

• Duration of corticosteroid use

  Up to Day 35 after initiation of methylene blue treatment

• Proportion of Participants Requiring Vasopressors

  Up to Day 35 after initiation of methylene blue treatment

• Duration of Vasopressor Therapy

  Up to Day 35 after initiation of methylene blue treatment

Study Arms (1)

Adjunctive Methylene Blue Dose-Escalation in Immunotherapy-related CRS and ICANS

EXPERIMENTAL

To evaluate the efficacy and safety of adjunctive methylene blue in the treatment of immunotherapy-related cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients receiving CAR-T or bispecific antibody therapy, using a 3+3 dose-escalation Phase I design.

Drug: Methylene Blue

Interventions

Methylene Blue DRUG

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.

Adjunctive Methylene Blue Dose-Escalation in Immunotherapy-related CRS and ICANS

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Cytokine Release Syndrome

Interventions

Methylene Blue

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Phenothiazines; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jianxiang Wang

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxiang Wang

CONTACT

+862223909120; wangjx@ihcams.ac

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 11, 2025
• Study Start: June 28, 2025
• Primary Completion (Estimated): June 28, 2028
• Study Completion (Estimated): June 28, 2030
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

CN (1)