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

NCT ID: NCT05905328

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-28
• Study Completion Date: 2027-06-30

Brief 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.

Detailed Description

The first phase of the study will be an open-label, dose escalation, safety assessment in a group of patients, and will also collect data to investigate the potential benefit of CTO1681, initiated prior to CAR T-cell therapy, in preventing or reducing certain toxicities or side effects associated with CAR T-cell therapy, such as cytokine release syndrome (CRS).

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.

Participants will provide blood samples at specified points throughout the study. In addition, urine samples, ECGs, scans, and other medical evaluations will be performed that are associated with the CAR T-cell therapy and/or necessary to verify study eligibility. Participants will be monitored for safety and efficacy for 43 days, and then will have follow-up to continue to monitor for safety and monitor for tumor response for up to 6 months for phase 1.

Conditions

Cytokine Release Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CTO1681 30 μg Total Daily Dose

Participants receive 10 μg CTO1681 orally 3 times daily (total daily dose of 30 μg) for 15 days.

Group Type: EXPERIMENTAL

CTO1681 10 μg

Intervention Type: DRUG

Administered 3 times daily for 15 days (initial cohort).

CTO1681 60 μg Total Daily Dose

Participants receive 20 μg CTO1681 orally 3 times daily (total daily dose of 60 μg) for 15 days.

Group Type: EXPERIMENTAL

CTO1681 20 μg

Intervention Type: DRUG

Administered 3 times daily for 15 days (successive cohort).

CTO1681 90 μg Total Daily Dose

Participants receive 30 μg CTO1681 orally 3 times daily (total daily dose of 90 μg) for 15 days.

Group Type: EXPERIMENTAL

CTO1681 30 μg

Intervention Type: DRUG

Administered 3 times daily for 15 days (successive cohort).

Interventions

CTO1681 10 μg

Administered 3 times daily for 15 days (initial cohort).

Intervention Type: DRUG

CTO1681 20 μg

Administered 3 times daily for 15 days (successive cohort).

Intervention Type: DRUG

CTO1681 30 μg

Administered 3 times daily for 15 days (successive cohort).

Intervention Type: DRUG

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CytoAgents, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arthur Bertolino, MD, PhD, MBA

Role: STUDY_CHAIR

CytoAgents, Inc.

Locations

University of California, Irvine - Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status: RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Site Status: RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Duke Cancer Institute

Durham, North Carolina, United States

Site Status: RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Arthur Bertolino, MD, PhD, MBA

Role: CONTACT

abertolino@cytoagents.com

616-928-1145

Heather Nottingham, PhD

Role: CONTACT

heather@tekteam.net

Facility Contacts

Blake Johnson

Role: primary

blakej@hs.uci.edu

714-456-3476

Rebecca Paynter, MSN, RN

Role: primary

rpaynter@augusta.edu

706-446-5177

Jon Arnason, MD

Role: primary

jarnason@bidmc.harvard.edu

617-667-9920

Jennifer Tichon, BSN, RN

Role: primary

jennifer.tichon@duke.edu

919-660-7262

Linda Elias, BSN, RN

Role: primary

eliaslj@upmc.edu

412-623-6037

Immunotherapy Intake

Role: primary

immunotherapy@fredhutch.org

206-606-4668

Other Identifiers

CTA-2101

Identifier Type: -

Identifier Source: org_study_id