Study of CTO1681 for the Prevention and Treatment of CRS in DLBCL Patients Receiving CAR T-Cell Therapy

Inclusion Criteria

• 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.

Exclusion Criteria

• Any cytotoxic chemotherapy within 14 days prior to leukapheresis.
• Clinically significant malabsorption syndromes and swallowing difficulties which are inadequately controlled with medication (eg, odynophagia, dysphagia, gastroesophageal reflux disease) as per Investigator assessment.
• Grade 2 or greater electrolyte imbalance, per CTCAE v5.0:
• Potassium < 3.0 or > 5.5 mmol/L
• Sodium < 130 or > 150 mmol/L
• Calcium < 8.0 or > 11.5 mg/dL
• Magnesium < 0.5 or > 1.23 mmol/L
• Clinically significant ECG abnormality at Screening or Baseline (Day -1), including but not limited to, a confirmed QTcF value > 470 msec. Patients to be excluded included those with QTcF readings that are borderline or difficult to interpret because of a condition such as bundle branch block, or in those where the end of the T wave is difficult to measure. This also includes any Grade 2 or greater conduction block disorder, atrial, or ventricular arrythmia.
• History of clinically significant arrhythmia and/or requiring anticoagulation/antiplatelet treatment at therapeutic dose.
• Any clinically significant (ie, active) cardiovascular disease, including cerebral vascular accident/stroke (< 6 months before enrollment), myocardial infarction (< 6 months before enrollment) or unstable angina, and congestive heart failure ≥ New York Heart Association Classification Class III.
• Uncontrolled thromboembolic events or recent severe hemorrhage within the last 6 months.
• Known history of any bleeding disorder.
• Requirement for ongoing therapeutic doses of anticoagulant therapy, antiplatelet or fibrinolytic agents (low molecular weight heparin prophylaxis is allowed).
• Baseline systolic blood pressure <100 mmHg.
• History of autoimmune disease/ graft versus host disease requiring immunosuppressive therapy within the last 2 years. However, physiologic steroids (prednisone equivalent) may be given at a dose of 5 mg or less.
• Patients who, in the opinion of the Investigator, would be unlikely to comply with study procedures or are otherwise unsuitable for enrollment.