CTO1681 for Preventing Side Effects in Cancer Therapy
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: CytoAgents, Inc.
Must not be taking: Anticoagulants, Antiplatelets
Disqualifiers: Arrhythmia, Cardiovascular disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot be on ongoing therapeutic doses of anticoagulant therapy, antiplatelet, or fibrinolytic agents, except for low molecular weight heparin prophylaxis.
What evidence supports the effectiveness of the drug CTO1681 in preventing side effects in cancer therapy?
Research shows that similar treatments, like TRAIL/Apo2L combined with certain chemotherapy drugs, can selectively target and kill cancer cells without harming normal cells. This suggests that CTO1681, if it works similarly, might help reduce side effects by sparing healthy cells during cancer treatment.12345
Is CTO1681 safe for humans?
Research Team
AB
Arthur Bertolino, MD, PhD, MBA
Principal Investigator
CytoAgents, Inc.
Eligibility Criteria
Adults with DLBCL who are set to receive CD19-directed CAR T-cell therapy and meet specific health criteria, such as adequate organ function and blood counts. They must not have certain heart conditions or uncontrolled bleeding disorders, be on high-dose anticoagulants, or have had recent chemotherapy.Inclusion Criteria
I am 18 years old or older.
My DLBCL has returned or didn't respond after my first treatment.
I meet all requirements for CAR T-cell therapy as per my hospital's rules.
See 2 more
Exclusion Criteria
I haven't had chemotherapy in the last 14 days.
I don't have major issues with absorbing food or swallowing that medication can't fix.
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, 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
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive CTO1681 three times daily for 15 days, starting just prior to CAR T-cell therapy
2 weeks
Multiple visits for blood samples and medical evaluations
Safety Monitoring
Participants are monitored for safety and efficacy for 43 days post-treatment
6 weeks
Regular visits for safety assessments
Follow-up
Participants are monitored for safety and tumor response for up to 6 months
6 months
Periodic visits for follow-up assessments
Treatment Details
Interventions
- CTO1681 (CAR T-cell Therapy)
Trial OverviewCTO1681 is being tested in three different doses to see if it can prevent or lessen the severity of cytokine release syndrome (CRS) caused by CAR T-cell therapy in patients with DLBCL. The trial starts with an open-label phase where everyone gets the drug before their cell therapy.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: CTO1681 90 μg Total Daily DoseExperimental Treatment1 Intervention
Participants receive 30 μg CTO1681 orally 3 times daily (total daily dose of 90 μg) for 15 days.
Group II: CTO1681 60 μg Total Daily DoseExperimental Treatment1 Intervention
Participants receive 20 μg CTO1681 orally 3 times daily (total daily dose of 60 μg) for 15 days.
Group III: CTO1681 30 μg Total Daily DoseExperimental Treatment1 Intervention
Participants receive 10 μg CTO1681 orally 3 times daily (total daily dose of 30 μg) for 15 days.
Find a Clinic Near You
Who Is Running the Clinical Trial?
CytoAgents, Inc.
Lead Sponsor
Trials
1
Recruited
50+
TFS HealthScience
Collaborator
Trials
1
Recruited
50+
Findings from Research
Ipilimumab, an anti-CTLA-4 antibody, has been shown to improve survival in patients with unresectable or metastatic melanoma, with a standard dosing of 3 mg/kg every 3 weeks for a total of 4 doses.
While ipilimumab can cause immune-related adverse events in 15% of patients, most are mild and manageable; however, high-grade events can be serious and require careful monitoring and treatment with corticosteroids.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Ipilimumab for advanced melanoma: a pharmacologic perspective.Trinh, VA., Hagen, B.[2021]
LCL161, an experimental drug that targets inhibitor of apoptosis proteins to promote cancer cell death, was well tolerated at doses up to 1,800 mg in a study involving 53 patients with advanced solid tumors.
The study found that while no patients had an objective response, LCL161 showed significant pharmacodynamic activity by degrading IAP1 protein and increasing cytokine levels, suggesting it has potential for further investigation despite the absence of direct tumor responses.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors.Infante, JR., Dees, EC., Olszanski, AJ., et al.[2021]
DEBIO1143, an antagonist of inhibitor apoptosis proteins, was well tolerated in a first-in-man study with 31 patients, showing no maximum tolerated dose (MTD) up to 900 mg and only one dose-limiting toxicity reported at 180 mg.
The drug demonstrated pharmacodynamic effects, such as increased plasma CCL2 and decreased cIAP-1 levels, at doses greater than 80 mg, but only 17% of patients achieved stable disease, suggesting it may be more effective as an adjunct treatment rather than a standalone therapy.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.Hurwitz, HI., Smith, DC., Pitot, HC., et al.[2021]
References
Selective and nonselective toxicity of TRAIL/Apo2L combined with chemotherapy in human bone tumour cells vs. normal human cells. [2016]
A phase I study of Topotecan, as a radiosensitizer, for thoracic malignancies. [2019]
HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death in multiple tumour types in vitro and in vivo. [2022]
Role of the microenvironment for radiosensitization by patupilone. [2012]
Pretreatment with paclitaxel enhances apo-2 ligand/tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of prostate cancer cells by inducing death receptors 4 and 5 protein levels. [2015]
Ipilimumab for advanced melanoma: a pharmacologic perspective. [2021]
Evaluation of current practice: management of chemotherapy-related toxicities. [2011]
Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies. [2022]
The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients. [2022]
Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. [2021]
Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. [2021]
Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study. [2021]
EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828. [2022]
Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system. [2018]
Modulation of apoptosis signaling in etoposide-treated lymphoma cells. [2013]