Using CTO1681 to prevent cytokine release syndrome 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

This study is testing if a new drug called CTO1681 can help prevent serious side effects in adults with diffuse large B-cell lymphoma who are getting CAR T-cell therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: CytoAgents, Inc. (Industry-sponsored)
• Drugs / interventions: CAR T, chemotherapy, prednisone
• Locations: 6 sites (Orange, California and 5 other locations)
• Trial ID: NCT05905328 on ClinicalTrials.gov

What this trial studies

This interventional study evaluates the effectiveness of CTO1681 in preventing or reducing cytokine release syndrome (CRS) in adult patients with diffuse large B-cell lymphoma (DLBCL) who are scheduled to receive CD19-directed CAR T-cell therapy. The study consists of two phases, with the first phase being an open-label, dose escalation safety assessment. Participants will start taking CTO1681 just before their CAR T-cell therapy and continue for 15 days, during which various medical evaluations and sample collections will occur to monitor safety and efficacy. The study aims to gather data on the potential benefits of CTO1681 in mitigating CAR T-cell therapy-related toxicities.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 years or older with relapsed or refractory DLBCL who are scheduled to receive CAR T-cell therapy without corticosteroid prophylaxis.

Not a fit: Patients who have not undergone leukapheresis or those with significant comorbidities affecting organ function may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could significantly reduce the incidence and severity of cytokine release syndrome in patients undergoing CAR T-cell therapy.

How similar studies have performed: Other studies have explored interventions for managing CRS in CAR T-cell therapy, but the specific use of CTO1681 is a novel approach.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older.
2. 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.
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.

Exclusion Criteria:

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 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.
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.

Where this trial is running

Orange, California and 5 other locations

• University of California, Irvine - Chao Family Comprehensive Cancer Center — Orange, California, United States (Recruiting)
• Georgia Cancer Center at Augusta University — Augusta, Georgia, United States (Recruiting)
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)
• Duke Cancer Institute — Durham, North Carolina, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Study coordinator: Gail Brown, MD

Conditions Cytokine Release Syndrome; Cytokine release syndrome; Cytokine storm; Hypercytokinemia; Immunotoxicity; CAR T-cell therapy