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

Open to people ages 18 years and up

1. Age 18 years or older.
2. Undergone leukapheresis and is scheduled to receive protocol-specified commercially available axicabtagene ciloleucel CD19-directed CAR T-cell therapy 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.
3. Met all inclusion criteria for CAR T-cell therapy per institutional guidelines.
4. Adequate organ function defined as:
   1. Estimated Creatinine Clearance per Cockroft Gault formula ≥ 60 mL/min.
   2. Serum alanine aminotransferase/aspartate aminotransferase ≤ 2.5 × ULN.
   3. Total bilirubin ≤ 1.5 × ULN.
   4. Left ventricular ejection fraction ≥ 40% on echocardiogram or multigated acquisition and no clinically significant pericardial effusion.
   5. Platelets ≥ 50,000/mm3.
   6. Absolute neutrophil count > 1000/μL.
   7. Absolute lymphocyte count > 100/μL.
5. Documented measurable lymphoma disease adequate to judge by Lugano Criteria.
6. Eastern Cooperative Oncology Group performance status 0 to 1.
7. 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.
8. 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.

1. Any cytotoxic chemotherapy within 14 days prior to leukapheresis.
2. Clinically significant malabsorption syndromes and swallowing difficulties which are inadequately controlled with medication (eg, odynophagia, dysphagia, gastroesophageal reflux disease) as per Investigator assessment.
3. Grade 2 or greater electrolyte imbalance, per CTCAE v5.0:
   1. Potassium < 3.0 or > 5.5 mmol/L
   2. Sodium < 130 or > 150 mmol/L
   3. Calcium < 8.0 or > 11.5 mg/dL
   4. Magnesium < 0.5 or > 1.23 mmol/L
4. Clinically significant ECG abnormality at Screening or Baseline (Day -1), including but not limited to, a confirmed QTcF value > 470 msec. Patients 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 will be excluded. This also includes any Grade 2 or greater conduction block disorder, atrial, or ventricular arrythmia.
5. History of clinically significant arrhythmia and/or requiring anticoagulation/antiplatelet treatment at therapeutic dose.
6. 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.
7. Uncontrolled thromboembolic events or recent severe hemorrhage within the last 6 months.
8. Known history of any bleeding disorder.
9. Requirement for ongoing therapeutic doses of anticoagulant therapy, antiplatelet or fibrinolytic agents (low molecular weight heparin prophylaxis is allowed).
10. Baseline systolic blood pressure <100 mmHg.
11. 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.
12. Patients who, in the opinion of the Investigator, would be unlikely to comply with study procedures or are otherwise unsuitable for enrollment.