CTO1681 10 µg: Administered 3 times daily for 15 days (initial cohort).
CTO1681 20 μg: Administered 3 times daily for 15 days (successive cohort).
CTO1681 30 μg: Administered 3 times daily for 15 days (successive cohort).
CTO1681 10 µg Run-in / 20 µg Treatment: Administered 3 times daily for up to 21 days (successive cohort).
CTO1681 20 µg Run-in / 30 µg Treatment: Administered three times daily for up to 21 days (successive cohort).
Study 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 lymphoma or multiple myeloma who are scheduled to receive CAR T-cell therapy.
The first phase of the study is open label with dose escalation. Participants will start taking CTO1681 either the day before starting lymphodepleting chemotherapy or just prior to receiving their CAR T-cell therapy, depending on their cohort assignment. In both cases participants will continue to take the study drug three times daily until 13 days after their CAR T-cell infusion.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Age 18 years or older.
2. Undergone leukapheresis and is scheduled to receive protocol-specified CAR T-cell therapy (axicabtagene ciloleucel, lisocabtagene maraleucel, idecabtagene vicleucel, or ciltacabtagene autoleucel) for relapsed or refractory lymphoma or multiple myeloma. All patients must have relapsed or refractory disease to at least one prior line of systemic therapy. Prior CAR T-cell therapy is allowable with approval from the Sponsor and Medical Monitor.
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. Disease specification must match the indication described in the product label of the planned CAR T-cell product.
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. A patient with an ECG abnormality may be enrolled only after approval by the Medical Monitor and Sponsor.
5. Active central nervous system (CNS) lymphoma (history of CNS involvement may be allowable only after approval by the Medical Monitor and Sponsor).
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 may be given at a dose of 5 mg or less (prednisone equivalent).
12. Patients who, in the opinion of the Investigator, would be unlikely to comply with study procedures or are otherwise unsuitable for enrollment.
13. Planned prophylactic treatment for CRS or ICANS with corticosteroids or any immunomodulatory or anticytokine therapies (including but not limited to tocilizumab and anakinra).
Primary outcome measure(s)
Incidence of adverse events (AEs) — 6 months following start of treatment AEs graded by CTCAE v5.0
Trial sites (6)
Facility
City
Region
Status
University of California, Irvine - Chao Family Comprehensive Cancer Center
Orange
California
Recruiting
Georgia Cancer Center at Augusta University
Augusta
Georgia
Recruiting
Beth Israel Deaconess Medical Center
Boston
Massachusetts
Recruiting
Duke Cancer Institute
Durham
North Carolina
Recruiting
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
Recruiting
Fred Hutchinson Cancer Center
Seattle
Washington
Recruiting
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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