Phase 1B/2A Study of CTO1681 for the Prevention and Treatment of Cytokine Release Syndrome in Patients With Diffuse Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy
This is an interventional study to evaluate the use of CTO1681 in preventing or reducing CAR T-cell-induced toxicities like cytokine release syndrome (CRS). This study will enroll adult patients with DLBCL who are scheduled to receive CD19-directed CAR T-cell therapy. The first phase of the study will be open label with dose escalation. Participants will start taking CTO1681 just prior to receiving their CAR T-cell therapy and continue to take the study drug three times daily for a total of 15 days.
• Age 18 years or older.
• Undergone leukapheresis and is scheduled to receive protocol-specified commercially available CD19-directed CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel) for DLBCL without corticosteroid prophylaxis for CRS and/or ICANS. Patients eligible for study must have relapsed or refractory DLBCL after at least one prior line of systemic therapy.
• Met all inclusion criteria for CAR T-cell therapy per institutional guidelines.
• Adequate organ function defined as:
‣ Estimated Creatinine Clearance per Cockroft Gault formula ≥ 60 mL/min.
⁃ Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × ULN.
⁃ Total bilirubin ≤ 1.5 × ULN.
⁃ Left ventricular ejection fraction ≥ 40% on echocardiogram or multigated acquisition and no clinically significant pericardial effusion.
⁃ Platelets ≥ 50,000/mm3.
⁃ Absolute neutrophil count \> 1000/μL.
⁃ Absolute lymphocyte count \> 100/μL.
• Documented measurable lymphoma disease adequate to judge by Lugano Criteria.
• Eastern Cooperative Oncology Group performance status 0 to 1.
• Female participants of childbearing potential and all male participants must agree to use Investigator-approved methods of birth control while on study drug and for 30 days thereafter.
• Patients who are willing to provide written informed consent before the predose procedures, or patients who have a legal representative capable of providing informed consent on their behalf.