Cytokine Release SyndromePhase 1NCT07169487
Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study
A Phase 1 study testing Methylene Blue in people with Cytokine Release Syndrome and ICANS, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cytokine Release Syndrome, ICANS
- What is being tested?
- Methylene Blue
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 28 Jun 2025to 28 Jun 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality
Jianxiang Wang, 022-23909120, wangjx@ihcams.ac.cn
Ying Wang
About this study
Official title: 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 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.
Read the detailed description
Methylene blue (MB), originally approved for methemoglobinemia, has demonstrated hemodynamic and neuroprotective effects. Preclinical data indicate that MB alleviates CRS/ICANS symptoms, protects blood-brain barrier integrity, limits microglial overactivation, and preserves T-cell antitumor function.
This Phase I, prospective, single-arm clinical trial will investigate MB as an adjunctive therapy for immunotherapy-related CRS and ICANS. Eligible patients are those receiving CAR-T cells or bispecific antibodies who subsequently develop Grade ≥1 CRS or ICANS, as defined by ASTCT 2019 criteria. Participants will be enrolled in a 3+3 dose-escalation schema with the following cohorts:
Cohort 1: 1 mg/kg once daily, intravenous infusion over 20 minutes Cohort 2: 2 mg/kg once daily, intravenous infusion over 20 minutes Cohort 3: 3 mg/kg once daily, intravenous infusion over 20 minutes Treatment will be administered for 3-5 consecutive days. Patients will undergo continuous assessment of vital signs (temperature, blood pressure, oxygen saturation), laboratory biomarkers (CRP, ferritin, cytokines), and neurotoxicity grading throughout therapy. Dosing adjustments will be based on real-time safety and efficacy evaluations.
Concomitant standard-of-care supportive interventions will be allowed, including tocilizumab (maximum of two doses), dexamethasone, ruxolitinib, cetuximab, and other symptomatic treatments. This trial seeks to establish the safety profile and preliminary efficacy of MB in mitigating immune therapy-related toxicities, potentially offering a novel strategy to improve the tolerability and safety of CAR-T and bispecific antibody therapies.
- Conditions
- Cytokine Release Syndrome, ICANS
- Being tested
- Methylene Blue
- Keywords
- Methylene Blue, Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, CAR-T Cell Therapy, Immunotherapy-Related Toxicity
- Medical subject headings
- Cytokine Release Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylene BlueDrug
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 group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Methylene Blue |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: Baseline to Day 35 post-treatment initiation
Secondary outcomes (5)
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.
Measured: Up to Day 35 after initiation of methylene blue treatment
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.
Measured: Up to Day 35 after initiation of methylene blue treatment
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.
Measured: Up to Day 35 after initiation of methylene blue treatment
Proportion of Participants Requiring Vasopressors
Percentage of participants who required vasopressor therapy at any time after initiation of methylene blue treatment.
Measured: Up to Day 35 after initiation of methylene blue treatment
Duration of Vasopressor Therapy
Total number of days participants received vasopressor therapy after initiation of methylene blue treatment.
Measured: Up to Day 35 after initiation of methylene blue treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2025
- Study start28 Jun 2025
- Primary completion28 Jun 2028 (estimated)
- Study completion28 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytokine Release SyndromeStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jianxiang Wang, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07169487
- Sponsor's protocol ID
- IIT2025072
- Status last verified
- Sep 2025
- First submitted
- 26 Aug 2025
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07169487
- Acronym / sponsor ID
- IIT2025072
- Conditions
- Cytokine Release Syndrome, ICANS
- Keywords
- Methylene Blue, Cytokine Release Syndrome, Immune Effector Cell-Associated Neurotoxicity Syndrome, CAR-T Cell Therapy, Immunotherapy-Related Toxicity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 28 Jun 2025 (actual)
- Primary completion
- 28 Jun 2028 (estimated)
- Study completion
- 28 Jun 2030 (estimated)
- First posted
- 11 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Methylene blue (MB), originally approved for methemoglobinemia, has demonstrated hemodynamic and neuroprotective effects. Preclinical data indicate that MB alleviates CRS/ICANS symptoms, protects blood-brain barrier integrity, limits microglial overactivation, and preserves T-cell antitumor function.
This Phase I, prospective, single-arm clinical trial will investigate MB as an adjunctive therapy for immunotherapy-related CRS and ICANS. Eligible patients are those receiving CAR-T cells or bispecific antibodies who subsequently develop Grade ≥1 CRS or ICANS, as defined by ASTCT 2019 criteria. Participants will be enrolled in a 3+3 dose-escalation schema with the following cohorts:
Cohort 1: 1 mg/kg once daily, intravenous infusion over 20 minutes Cohort 2: 2 mg/kg once daily, intravenous infusion over 20 minutes Cohort 3: 3 mg/kg once daily, intravenous infusion over 20 minutes Treatment will be administered for 3-5 consecutive days. Patients will undergo continuous assessment of vital signs (temperature, blood pressure, oxygen saturation), laboratory biomarkers (CRP, ferritin, cytokines), and neurotoxicity grading throughout therapy. Dosing adjustments will be based on real-time safety and efficacy evaluations.
Concomitant standard-of-care supportive interventions will be allowed, including tocilizumab (maximum of two doses), dexamethasone, ruxolitinib, cetuximab, and other symptomatic treatments. This trial seeks to establish the safety profile and preliminary efficacy of MB in mitigating immune therapy-related toxicities, potentially offering a novel strategy to improve the tolerability and safety of CAR-T and bispecific antibody therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adjunctive Methylene Blue Dose-Escalation in Immunotherapy-related CRS and ICANS | Experimental | Drug: Methylene BlueTo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Methylene BlueIntravenous 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. | Drug | Adjunctive Methylene Blue Dose-Escalation in Immunotherapy-related CRS and ICANS |
Primary outcome
Incidence and type of methylene blue-related serious adverse events (SAEs)
Time frame: 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
Time frame: 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
Time frame: 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).
5 secondary outcomes
Incidence of Grade ≥3 CRS and ICANS
Time frame: Up to Day 35 after initiation of methylene blue treatment
Duration of CRS and ICANS
Time frame: Up to Day 35 after initiation of methylene blue treatment
Duration of corticosteroid use
Time frame: Up to Day 35 after initiation of methylene blue treatment
Proportion of Participants Requiring Vasopressors
Time frame: Up to Day 35 after initiation of methylene blue treatment
Duration of Vasopressor Therapy
Time frame: Up to Day 35 after initiation of methylene blue treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jianxiang Wang principal investigator
Institute of Hematology & Blood Diseases Hospital, China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methylene Blue in people with Cytokine Release Syndrome and ICANS, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jianxiang Wang (+862223909120, wangjx@ihcams.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and type of methylene blue-related serious adverse events (SAEs) (time frame: Up to Day 35 after initiation of methylene blue treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.