Disulfiram for Preventing Treatment Complications in Patients Undergoing CAR T-cell Therapy for Relapsed or Refractory Diffuse Large B-cell Lymphoma

November 5, 2026 updated by: University of Michigan Rogel Cancer Center

A Single Center, Phase I/II Study of Disulfiram for the Prevention of Immunotoxicity in Patients Undergoing CAR T-Cell Therapy

This phase I/II trial tests the safety, best dose, and effectiveness of disulfiram for preventing treatment complications in patients with large B-cell lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory) and who are undergoing chimeric antigen receptor (CAR) T-cell therapy. Two major complications of CAR T-cell therapy include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS results from inflammation in the body when the immune system responds too aggressively to the modified T cells working to attack cancer cells. ICANS is inflammation of the brain or nerves. CRS is most often a prelude to ICANS, and both of these toxicities currently require immunosuppression for treatment, which can inhibit CAR T-cell response. Disulfiram has been found to impact several biologic pathways that cause CRS. Disulfiram may be safe and effective for reducing the incidence and severity of reactions to CAR T-cell therapy without inhibiting CAR T-cell response.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Rogel Cancer Center
        • Contact:
        • Principal Investigator:
          • Marcus Geer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologic diagnosis of relapsed/refractory large B-cell lymphoma
  • >= 18 years of age at the time of signing informed consent (ICF)
  • Understands and voluntarily signs the ICF prior to conduct of any study-related assessments or procedures
  • Willing to adhere to the study visit schedule and other protocol requirements
  • Willing/able to abstain from any drug/substance at risk for reaction with disulfiram for the duration of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Eligible for therapy with axicabtagene ciloleucel per institutional criteria
  • Confirmation of a manufactured CAR T-cell product within clinical specifications for axicabtagene ciloleucel
  • Females and males of childbearing potential must be willing to use effective methods of contraception from the time of informed consent until 12 months (female) or 4 months (males with female partners of reproductive potential) after the cyclophosphamide infusion
  • Willingness to consent / co-enroll on the University of Michigan cellular therapy long-term follow-up study - HUM00043287 (UMCC2001-0234)

Exclusion Criteria:

  • Serious or uncontrolled infection defined as not having cleared infection despite being on appropriate antimicrobial therapy for 5 days would be excluded. Also any infection which, in the opinion of the investigator, places the patient at an unacceptable risk for treatment-related complications, could impede the ability to safely administer therapy, or could interfere with evaluation of study intervention

  • Active hepatitis B or C (latent hepatitis B will not be excluded), or HIV. Entecavir prophylaxis can be used for latent hepatitis B. A patient's viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing at screening

  • Total bilirubin of >= 1.5 x upper limit of normal (ULN) unless attributed to Gilbert's syndrome or underlying primary malignancy. Patients with Gilbert syndrome or underlying primary malignancy involving the liver with total bilirubin >= 2.5 x ULN (or absolute total bilirubin >= 3 mg/dL) should be excluded. Aspartate aminotransferase (AST): >= 2.5 x ULN, alanine aminotransferase (ALT): >= 2.5 x ULN

  • Active concurrent autoimmune disease requiring systemic immunosuppression

  • Active primary or secondary central nervous system (CNS) lymphoma

  • Active clinically relevant central nervous system disease including but not limited to:

    • Seizures/Epilepsy
    • Stroke or unstable neurologic deficits within the past 12 months prior to enrollment
    • Cerebral edema
    • Aphasia
    • Severe brain injury
    • Cerebellar disease
    • Documented history of dementia as confirmed by neuropsychiatric testing
    • Parkinson's disease
    • Psychosis

  • Any other significant medical condition (including neurological or psychiatric) which, in the opinion of the investigator, places the participant at an unacceptable risk for treatment-related complications, could interfere with the successful or safe delivery of therapy, or could interfere with evaluation of study intervention or interpretation of participant safety or study results. Including but not limited to:

    • Diabetes with associated autonomic dysfunction
    • Uncontrolled Hypothyroidism
    • Chronic or acute nephritis
    • Hepatic cirrhosis/insufficiency

  • Pregnant or nursing females

  • Current or previous treatment with any other agents explicitly for prophylaxis of CRS or ICANS, including corticosteroids and investigational agents during the study enrollment period. Corticosteroids given for disease treatment should have a washout of at least 5 half-lives prior to cell infusion. Use of prophylactic antiseizure medications is not contraindicated

  • History of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study

  • Concurrent use of prohibited medications or substances at risk of precipitating a disulfiram reaction

  • Hypersensitivity to disulfiram or to other thiuram derivatives used in pesticides and rubber vulcanization

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Supportive care (disulfiram)

Patients receive disulfiram PO QD on days -5 to +21. Patients receive cyclophosphamide IV and fludarabine IV on days -5 to -3 and then receive axi-cel IV on day 0. Patients also undergo CT or PET/CT at screening and follow-up and undergo collection of blood samples throughout the trial.
Drug: Cyclophosphamide

Given IV

Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Asta B 518
  • B-518
  • WR-138719
  • B 518
  • B518
  • WR 138719
  • WR138719
  • Frindovyx
Procedure: Biospecimen Collection

Undergo collection of blood samples

Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection
Procedure: Computed Tomography

Undergo CT or PET/CT

Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Procedure: Positron Emission Tomography

Undergo PET/CT

Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • PT
  • Positron emission tomography (procedure)
Drug: Fludarabine

Given IV

Other Names:
  • Fluradosa
Biological: Axicabtagene Ciloleucel

Given IV

Other Names:
  • Yescarta
  • KTE C19
  • KTE-C19
  • KTE-C19 CAR
  • Axi-cel
  • Axicel
  • KTEC19
Drug: Disulfiram

Given PO

Other Names:
  • Antabuse
  • DS
  • Teturamin
  • TTD
  • Tetraethylthioperoxydicarbonic Diamide

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicities
Time Frame: Within day +35 post-chimeric antigen receptor (CAR) T-cell therapy

At the end of the trial, will report number of patients assigned to each dose, as well as the number of patients experiencing toxicity at each dose.
Within day +35 post-chimeric antigen receptor (CAR) T-cell therapy
Proportion of patients that are alive and free from grade 2-4 cytokine release syndrome (CRS) with no intervening treatment of CRS
Time Frame: Through day +28 post-CAR T-cell therapy

At the end of the trial, will report number of patients assigned to each dose, as well as the number of patients experiencing efficacy outcomes at each dose.
Through day +28 post-CAR T-cell therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of grade 2-4 CRS
Time Frame: By day +28 post-CAR T-cell therapy

The occurrence of severe CRS will be considered binary, and the rate will be defined as number of patients with severe CRS divided by the number of evaluable patients. The rate will be reported along with the 95% exact binomial confidence interval.
By day +28 post-CAR T-cell therapy
Incidence of all-grade CRS
Time Frame: By day +28 post-CAR T-cell therapy

The occurrence of CRS will be considered binary, and the rate will be defined as number of patients with CRS divided by the number of evaluable patients. The rate will be reported along with the 95% exact binomial confidence interval.
By day +28 post-CAR T-cell therapy
Incidence of all-grade immune effector cell associated neurotoxicity syndrome (ICANS)
Time Frame: By day +28 post-CAR T-cell therapy

The occurrence of severe ICANS will be considered binary and the rate will be defined as number of patients with severe ICANS divided by the number of evaluable patients. The rate will be reported along with the 95% exact binomial confidence interval.
By day +28 post-CAR T-cell therapy
Incidence of disulfiram-related grade 2 to 5 non-hematologic toxicity
Time Frame: By day +28 post-CAR T-cell therapy

Will be assessed by Common Terminology Criteria for Adverse Events, version 5.0. The occurrence of drug related grade 2-5 non-hematologic toxicity with at least a 'possible' attribution to disulfiram will be considered binary, and the rate will be defined as number of patients experiencing toxicity divided by the number of evaluable patients. The rate will be reported along with the 95% exact binomial confidence interval.
By day +28 post-CAR T-cell therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Michigan Rogel Cancer Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marcus Geer, University of Michigan Rogel Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 12, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UMCC 2025.132
  • NCI-2026-05448 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • HUM00287270 (Other Identifier: University of Michigan Rogel Cancer Center)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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