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

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