Study of CTO1681 for the Prevention and Treatment of CRS in DLBCL Patients Receiving CAR T-Cell Therapy
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
CytoAgents, Inc.
54 participants
Dec 28, 2023
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria14
- 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.
- 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 Criteria16
- 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.
Interventions
Administered 3 times daily for 15 days (initial cohort).
Administered 3 times daily for 15 days (successive cohort).
Administered 3 times daily for 15 days (successive cohort).
Locations(6)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05905328