RECRUITING

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

Conditions

Cytokine Release Syndrome Cytokine storm Hypercytokinemia Immunotoxicity CAR T-cell therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-12-28

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05905328

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
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.

Inclusion Criteria

Exclusion Criteria

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.

Contacts and Locations

Study Contact

Arthur Bertolino, MD, PhD, MBA

CONTACT

6169281145

abertolino@cytoagents.com

Heather Nottingham, PhD

CONTACT

5305592319

heather@tekteam.net

Principal Investigator

Lee Schacter, MD

STUDY_DIRECTOR

TFS HealthScience

Study Locations (Sites)

University of California, Irvine - Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

United States

Duke Cancer Institute

Durham, North Carolina, 27705

United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232

United States

Fred Hutchinson Cancer Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: CytoAgents, Inc.

Lee Schacter, MD, STUDY_DIRECTOR, TFS HealthScience

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-12-28

Study Completion Date2027-06

Study Record Updates

Study Start Date2023-12-28

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Cytokine Release Syndrome