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

NCT05905328 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTA-2101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

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.

Conditions

Cytokine Release Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events (AEs)

  AEs graded by CTCAE v5.0

  6 months following start of treatment

Secondary Outcomes (8)

• Incidence of CRS (any grade)

  6 months following the start of treatment

• Incidence of ICANS (any grade)

  6 months following the start of treatment

• Incidence of hospitalizations

  6 months following the start of treatment

• Use of other anticytokine therapies

  6 months following the start of treatment

• Proinflammatory cytokine levels

  6 months following the start of treatment

Study Arms (3)

CTO1681 30 μg Total Daily Dose

EXPERIMENTAL

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

Drug: CTO1681 10 μg

CTO1681 60 μg Total Daily Dose

EXPERIMENTAL

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

Drug: CTO1681 20 μg

CTO1681 90 μg Total Daily Dose

EXPERIMENTAL

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

Drug: CTO1681 30 μg

Interventions

CTO1681 10 μg DRUG

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

CTO1681 30 μg Total Daily Dose

CTO1681 20 μg DRUG

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

CTO1681 60 μg Total Daily Dose

CTO1681 30 μg DRUG

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

CTO1681 90 μg Total Daily Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CytoAgents, Inc.: lead

Study Sites (6)

University of California, Irvine - Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Duke Cancer Institute

Durham, North Carolina, 27705, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Cytokine Release Syndrome

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Mike Howell, PhD

  CytoAgents, Inc.

  STUDY CHAIR

Central Study Contacts

Gail Brown, MD

CONTACT

650-868-2182; gail@tekteam.net

Heather Nottingham, PhD

CONTACT

heather@tekteam.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Phase 1b portion of the study is an open-label, dose-escalating, safety and pharmacokinetic (PK) study of multiple ascending doses of CTO1681 in patients with Diffuse Large B-cell Lymphoma who receive commercially available CD19-directed CAR T-cell therapy.

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: June 15, 2023
• Study Start: December 28, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)