Phase 1B/2A Study of CTO1681 for the Prevention and Treatment of Cytokine Release Syndrome in Patients 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 lymphoma or multiple myeloma who are scheduled to receive CAR T-cell therapy. The first phase of the study is open label with dose escalation. Participants will start taking CTO1681 either the day before starting lymphodepleting chemotherapy or just prior to receiving their CAR T-cell therapy, depending on their cohort assignment. In both cases participants will continue to take the study drug three times daily until 13 days after their CAR T-cell infusion.
• Age 18 years or older.
• Undergone leukapheresis and is scheduled to receive protocol-specified CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, idecabtagene vicleucel, or ciltacabtagene autoleucel) for relapsed or refractory lymphoma or multiple myeloma. All patients must have relapsed or refractory disease to at least one prior line of systemic therapy. Prior CAR T-cell therapy is allowable with approval from the Sponsor and Medical Monitor.
• 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.
• Disease specification must match the indication described in the product label of the planned CAR T-cell product.
• 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.