- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05905328
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
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Arthur Bertolino, MD, PhD, MBA
- Phone Number: 6169281145
- Email: abertolino@cytoagents.com
Study Contact Backup
- Name: Heather Nottingham, PhD
- Phone Number: 5305592319
- Email: heather@tekteam.net
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15219
- Recruiting
- Alison Sehgal
-
Principal Investigator:
- Alison Sehgal, MD
-
Contact:
- Linda Elias, BSN, RN
- Phone Number: 412-623-6037
- Email: eliaslj@upmc.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age 18 years or older.
- 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.
- Met all inclusion criteria for CAR T-cell therapy per institutional guidelines.
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 Criteria:
- 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 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CTO1681 30 μg Total Daily Dose
Participants receive 10 μg CTO1681 orally 3 times daily (total daily dose of 30 μg) for 15 days.
|
Administered 3 times daily for 15 days (initial cohort).
|
Experimental: CTO1681 60 μg Total Daily Dose
Participants receive 20 μg CTO1681 orally 3 times daily (total daily dose of 60 μg) for 15 days.
|
Administered 3 times daily for 15 days (successive cohort).
|
Experimental: CTO1681 90 μg Total Daily Dose
Participants receive 30 μg CTO1681 orally 3 times daily (total daily dose of 90 μg) for 15 days.
|
Administered 3 times daily for 15 days (successive cohort).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events (AEs)
Time Frame: 6 months following start of treatment
|
AEs graded by CTCAE v5.0
|
6 months following start of treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of CRS (any grade)
Time Frame: 6 months following the start of treatment
|
CRS graded by ASTCT Consensus Grading
|
6 months following the start of treatment
|
Incidence of ICANS (any grade)
Time Frame: 6 months following the start of treatment
|
ICANS graded by ASTCT Consensus Grading
|
6 months following the start of treatment
|
Incidence of hospitalizations
Time Frame: 6 months following the start of treatment
|
Unplanned hospitalizations
|
6 months following the start of treatment
|
Use of other anticytokine therapies
Time Frame: 6 months following the start of treatment
|
Use of cytokine mitigating therapies other than CTO1681
|
6 months following the start of treatment
|
Proinflammatory cytokine levels
Time Frame: 6 months following the start of treatment
|
Concentration of proinflammatory cytokines in the blood
|
6 months following the start of treatment
|
Concentration of CTO1681
Time Frame: Baseline, Day 0, Day 2, Day 4, Day 6, Day 13
|
Concentration of CTO1681 in the blood
|
Baseline, Day 0, Day 2, Day 4, Day 6, Day 13
|
CAR T-cell concentration in blood
Time Frame: 6 months following the start of treatment
|
Concentration of CAR T-cell measured using ddPCR
|
6 months following the start of treatment
|
CAR T-cell antitumor response
Time Frame: 6 months following the start of treatment
|
Antitumor response assessment using the Lugano Criteria
|
6 months following the start of treatment
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Peter J Larson, MD, TFS HealthScience
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTA-2101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cytokine Release Syndrome
-
University of PennsylvaniaRecruitingCRS - Cytokine Release Syndrome | HLHUnited States
-
Rigshospitalet, DenmarkNot yet recruitingHematologic Cancer | CRS - Cytokine Release Syndrome
-
Medical University InnsbruckCompletedSepsis | Septic Shock | Cytokine Storm | Cytokine Release Syndrome | CatecholamineAustria
-
Mahidol UniversityFaculty of Medicine Siriraj HospitalRecruitingSeptic Shock | Cytokine StormThailand
-
University of ZurichCytoSorbents Europe GmbHCompletedSeptic Shock | Cytokine Storm
-
Université de SherbrookeCentre de recherche du CHUSRecruitingLiver Transplantation | Kidney Transplantation | Organ Donation | Graft DysfunctionCanada
-
Applied Science Private UniversityCompletedCytokine Storm | CytokinesJordan
-
Aretaieion University HospitalCompletedSurgery | Cytokine Storm | Infection After Transfusion | Transfusion-related Immunomodulation ReactionGreece
-
Federal University of São PauloCompletedInflammation | Burns | Cytokine Storm | Growth Factors, Combined Defect ofBrazil
-
Ministry of Health, Saudi ArabiaFaculty of medicine kafr elshiekh universityNot yet recruitingDHA as Antioxidant Anti-inflammatory Immunomodulation , Overcome Cytokine StormSaudi Arabia, Egypt
Clinical Trials on CTO1681 10 μg
-
AllerganTerminatedGastroparesisUnited States, Spain, Italy, Australia, Russian Federation, Canada, India, Thailand, France, Malaysia, Denmark, Korea, Republic of, Bulgaria, Germany, Poland, Singapore, Mexico, Israel, Philippines, Ukraine, Belgium, South Africa, A... and more
-
Peptinov SASRecruitingKnee OsteoarthritisFrance
-
Chang Gung Memorial HospitalNational Science Council, TaiwanCompleted
-
Trinomab Biotech Co., Ltd.TIGERMED AUSTRALIA PTY LIMITEDCompletedHealthy Adult SubjectsAustralia
-
Baylor College of MedicineGeorge Washington University; Children's National Research InstituteCompletedHookworm Infection | Hookworm DiseaseUnited States
-
Leiden University Medical CenterGöteborg University; Walter Reed Army Institute of Research (WRAIR); PATH; European... and other collaboratorsNot yet recruitingShigellosis | Bacillary DysenteryNetherlands
-
PfizerJANSSEN Alzheimer Immunotherapy Research & Development, LLCCompletedAlzheimer's DiseaseUnited States
-
Alebund Pty LtdCompletedHealthy SubjectsAustralia
-
GlaxoSmithKlineCompletedCOVID-19 | SARS-CoV-2Australia, United States, Philippines
-
Alebund PharmaceuticalsNot yet recruiting