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Cytokine Release SyndromePhase 1/2NCT05905328

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

A Phase 1/2 study testing CTO1681 10 µg, CTO1681 20 μg and CTO1681 30 μg in people with Cytokine Release Syndrome, run by CytoAgents, Inc. at 6 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cytokine Release Syndrome
What is being tested?
CTO1681 10 µg, CTO1681 20 μg and CTO1681 30 μg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
6 sitesUnited States
Study dates
28 Dec 2023to Jun 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years or older.
  • 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.
  • 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.
Show all 15Show fewer
  • 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.
  • Disease specification must match the indication described in the product label of the planned CAR T-cell product.
  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • 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. A patient with an ECG abnormality may be enrolled only after approval by the Medical Monitor and Sponsor.
  • Active central nervous system (CNS) lymphoma (history of CNS involvement may be allowable only after approval by the Medical Monitor and Sponsor).
  • 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 may be given at a dose of 5 mg or less (prednisone equivalent).
  • Patients who, in the opinion of the Investigator, would be unlikely to comply with study procedures or are otherwise unsuitable for enrollment.
  • Planned prophylactic treatment for CRS or ICANS with corticosteroids or any immunomodulatory or anticytokine therapies (including but not limited to tocilizumab and anakinra).

Trial locations and contacts

6 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gail Brown, MD contact

650-868-2182

gail@tekteam.net

Heather Nottingham, PhD contact

heather@tekteam.net

6 sites in 1 country

United States6 sites, 6 recruiting

  • Georgia Cancer Center at Augusta University

    Augusta, Georgia, 30912

    Rebecca Paynter, MSN, RN, 7064465177, rpaynter@augusta.edu

    Yenny Moreno, MD

    Recruiting

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

    Jon Arnason, MD, 617-667-9920, jarnason@bidmc.harvard.edu

    Jon Arnason, MD

    Recruiting

  • Duke Cancer Institute

    Durham, North Carolina, 27705

    Jennifer Tichon, BSN, RN, 919-660-7262, jennifer.tichon@duke.edu

    Chenyu Lin, MD

    Recruiting

  • University of California, Irvine - Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Blake Johnson, 714-456-3476, blakej@hs.uci.edu

    Stefan Ciurea, MD

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

    Linda Elias, BSN, RN, 4126236037, eliaslj@upmc.edu

    Alison Sehgal, MD

    Recruiting

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

    Immunotherapy Intake, 206-606-4668, immunotherapy@fredhutch.org

    Jordan Gauthier, MD, MSc

    Recruiting

Other trials in United States

About this study

Official title: Phase 1B/2A Study of CTO1681 for the Prevention and Treatment of Cytokine Release Syndrome in Patients 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 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.

Read the 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). This study will enroll adult patients with lymphoma or multiple myeloma who are scheduled to receive commercially available, protocol specified CAR T-cell therapy.

Participants who are assigned to cohorts not receiving run-in dosing will start taking CTO1681 the day prior to receiving their CAR T-cell therapy and continue to take the study drug three times daily until 13 days after the CAR T-cell infusion (total of 15 days). Participants assigned to cohorts the do receive run-in dosing will start taking CTO1681 the day before starting lymphodepleting chemotherapy and continue to take the study drug three times daily until 13 days after the CAR T-cell infusion (approximately 20 days total).

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 from the start of dosing until 41 days after CAR T-cell infusion, 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.

Being tested
CTO1681 10 µg, CTO1681 20 μg, CTO1681 30 μg, CTO1681 10 µg Run-in / 20 µg Treatment, CTO1681 20 µg Run-in / 30 µg Treatment
Keywords
Cytokine release syndrome, Cytokine storm, Hypercytokinemia, Immunotoxicity, CAR T-cell therapy
Medical subject headings
Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CTO1681 10 µgDrug

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

  • CTO1681 20 μgDrug

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

  • CTO1681 30 μgDrug

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

  • CTO1681 10 µg Run-in / 20 µg TreatmentDrug

    Administered 3 times daily for up to 21 days (successive cohort).

  • CTO1681 20 µg Run-in / 30 µg TreatmentDrug

    Administered three times daily for up to 21 days (successive cohort).

Study groups in NCT05905328
Study groupRoleWhat they receive
CTO1681 30 μg Total Daily DoseExperimentalParticipants receive 10 μg CTO1681 orally 3 times daily (total daily dose of 30 μg) for 15 days.
Receives: Drug: CTO1681 10 µg
CTO1681 60 μg Total Daily DoseExperimentalParticipants receive 20 μg CTO1681 orally 3 times daily (total daily dose of 60 μg) for 15 days.
Receives: Drug: CTO1681 20 μg
CTO1681 90 μg Total Daily DoseExperimentalParticipants receive 30 μg CTO1681 orally 3 times daily (total daily dose of 90 μg) for 15 days.
Receives: Drug: CTO1681 30 μg
CTO1681 30 µg Run-in Daily Dose / 60 µg Treatment Daily DoseExperimentalParticipants receive 10 µg CTO1681 orally 3 times daily (total daily dose of 30 µg) during the run-in period and then 20 µg CTO1681 orally 3 times daily (total daily dose of 60 µg) during the treatment period. The total dosing duration is up to 21 days.
Receives: Drug: CTO1681 10 µg Run-in / 20 µg Treatment
CTO1681 60 µg Run-in Daily Dose / 90 µg Treatment Daily DoseExperimentalParticipants receive 20 µg CTO1681 orally 3 times daily (total daily dose of 60 µg) during the run-in period and then 30 µg CTO1681 orally 3 times daily (total daily dose of 90 µg) during the treatment period. The total dosing duration is up to 21 days.
Receives: Drug: CTO1681 20 µg Run-in / 30 µg Treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events (AEs)

    AEs graded by CTCAE v5.0

    Measured: 6 months following start of treatment

Secondary outcomes (8)

  1. Incidence of CRS (any grade)

    CRS graded by ASTCT Consensus Grading

    Measured: 6 months following the start of treatment

  2. Incidence of ICANS (any grade)

    ICANS graded by ASTCT Consensus Grading

    Measured: 6 months following the start of treatment

  3. Incidence of hospitalizations

    Unplanned hospitalizations

    Measured: 6 months following the start of treatment

  4. Use of other anticytokine therapies

    Use of cytokine mitigating therapies other than CTO1681

    Measured: 6 months following the start of treatment

  5. Proinflammatory cytokine levels

    Concentration of proinflammatory cytokines in the blood

    Measured: 6 months following the start of treatment

  6. Concentration of CTO1681

    Concentration of CTO1681 in the blood

    Measured: Baseline, Day 0, Day 2, Day 4, Day 6, Day 13

  7. CAR T-cell concentration in blood

    Concentration of CAR T-cell measured using ddPCR

    Measured: 6 months following the start of treatment

  8. CAR T-cell antitumor response

    Antitumor response assessment using the Lugano or International Myeloma Working Group (IMWG) Criteria

    Measured: 6 months following the start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2023
  2. Study start28 Dec 2023
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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 Lymphoma or Multiple Myeloma who receive commercially available, protocol specified CAR T-cell therapy.
Masking
None (open label)
Enrolment
54 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05905328
Sponsor's protocol ID
CTA-2101
Other IDs
R44CA295189
Status last verified
Aug 2026
First submitted
28 Apr 2023
Last updated
31 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CTO1681 10 µg, CTO1681 20 μg and CTO1681 30 μg in people with Cytokine Release Syndrome, run by CytoAgents, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gail Brown, MD (650-868-2182, gail@tekteam.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) (time frame: 6 months following start of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05905328.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.

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