Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitute of Hematology & Blood Diseases Hospital, China
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Methylene Blue
DrugIntravenous 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.
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: Adjunctive Methylene Blue Dose-Escalation in Immunotherapy-related CRS and ICANSExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Up to Day 35 after initiation of methylene blue treatment2
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.
Time frame
Up to Day 35 after initiation of methylene blue treatment3
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).
Time frame
Baseline to Day 35 post-treatment initiationSecondary outcomes
1
Incidence of Grade ≥3 CRS and ICANS
Proportion of participants who develop Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), assessed according to ASTCT 2019 grading criteria.
Time frame
Up to Day 35 after initiation of methylene blue treatment2
Duration of CRS and ICANS
The total duration (in days) of CRS and ICANS from onset until resolution to Grade 0, according to ASTCT 2019 criteria.
Time frame
Up to Day 35 after initiation of methylene blue treatment3
Duration of corticosteroid use
Total duration (in days) of systemic corticosteroid administration for the management of CRS and/or ICANS after initiation of methylene blue treatment.
Time frame
Up to Day 35 after initiation of methylene blue treatment4
Proportion of Participants Requiring Vasopressors
Percentage of participants who required vasopressor therapy at any time after initiation of methylene blue treatment.
Time frame
Up to Day 35 after initiation of methylene blue treatmentSponsors and contacts
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Source ClinicalTrials.gov