Non-Hodgkin LymphomaPhase 1NCT05044039
Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy
A Phase 1 study testing Duvelisib and CAR T-cells in people with Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia, run by Washington University School of Medicine at 1 site in United States.
Trial summary
While chimeric antigen receptor T-cell (CAR T-cell) therapy produces impressive response rates in heavily pre-treated patients, early loss of response remains a barrier. One potential mechanism of relapse is limited CAR T-cell persistence. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia
- What is being tested?
- Duvelisib and CAR T-cells
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2022to 22 May 2030
- Phase
- Phase 1
- 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
- Meets FDA-approved criteria for treatment of non-Hodgkin lymphoma (NHL) with axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), lisocabtagene maraleucel (Breyanzi) or brexucabtagene autoleucel (Tecartus). Subjects receiving breuxacabtagene autoleucel for treatment of B-cell acute lymphoblastic leukemia (ALL) are not eligible.
- At least 18 years of age.
- The effects of duvelisib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for at least 3 months after the last dose of duvelisib, as well as conform to institutional CAR T-cell guidelines. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for at least 3 months after the last dose of duvelisib.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- Receiving axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, or brexucabtagene autoleucel for the treatment of B-cell acute lymphoblastic leukemia.
- Known allergy or intolerance to duvelisib or another PI3K inhibitor. Previous treatment with duvelisib or other PI3K inhibitor is permitted unless therapy was discontinued due to toxicity or intolerance of therapy.
- Receiving therapy with a strong CYP3A inducer or inhibitor that cannot be discontinued during duvelisib therapy. Subjects receiving a strong CYP3A inducer or inhibitor at screening are eligible to participate if the drug can be discontinued the longest of the following time periods prior to initiation of duvelisib: 7 days (for strong CYP3A inhibitors), 14 days (for strong CYP3A inducers) or 4-5 half-lives (either inducer or inhibitor).
- Active CNS involvement by hematologic malignancy under treatment
- Evidence of uncontrolled infection of any origin (viral, bacterial, or fungal)
- Active bacterial, fungal or mycobacterial infection tuberculosis requiring treatment within the two years prior to study enrollment
Show all 20Show fewer
- Known HIV infection, untreated hepatitis C or hepatitis B infection. Untreated hepatitis B is not an exclusion if hepatitis B is undetectable.
- Acute or chronic GVHD requiring systemic therapy
- Concurrent use of chronic systemic steroids or immunosuppressant medications
- Known history of immunologic/autoimmune disease affecting the CNS unrelated to diagnosis of hematologic malignancy under treatment
- Clinically significant pulmonary disease, defined as grade 2 or greater dyspnea or grade 2 or greater hypoxia
- Clinically significant cardiac disease, defined as unstable angina, acute myocardial infarction in the last 6 months, and NYHA class II or IV heart failure. Subjects with unstable arrhythmias that are not stable with medical management in 2 weeks prior to day -2 are also excluded.
- Clinically significant hepatic disease, defined as ALT, AST or alkaline phosphatase ≥ 3x ULN or total bilirubin > 1.5x ULN (unless related to Gilbert's or Meulengracht's syndrome). Subjects with a history of chronic liver disease, previous veno-occlusive disease, active alcohol abuse or history of alcohol abuse within the past 6 months are also excluded.
- Clinically significant renal disease, defined as calculated or measured creatinine clearance < 50 mL/min
- Currently breastfeeding or pregnant. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
- Inability to swallow and retain oral medication or prior surgery or GI dysfunction that may affect drug absorption (i.e. gastric bypass surgery, gastrectomy)
- Receipt of a prior investigational agent within 4 weeks before Day -3 or currently receiving any other investigational agents.
- Unable to receive prophylactic treatment for pneumocystis, HSV or VZV at screening
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of medication, attendance of study visits, elevated risk of complications or interference with interpretation of the study data
- A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease. Non-metastatic, non-melanoma skin cancers are not considered exclusionary.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase I Dose Escalation and Dose Expansion Study of Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy
While chimeric antigen receptor T-cell (CAR T-cell) therapy produces impressive response rates in heavily pre-treated patients, early loss of response remains a barrier. One potential mechanism of relapse is limited CAR T-cell persistence. Pre-clinical research shows that PI3K inhibition represents an intriguing mechanism for increasing CAR T-cell persistence that is easily reversible and CAR T-cell agnostic. The investigators hypothesize that PI3K inhibition with duvelisib would be safe, may provide effective prophylaxis against cytokine release syndrome (CRS), and may enhance the persistence and efficacy of CAR T-cells in the treatment of hematologic malignancies.
- Conditions
- Non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia
- Being tested
- Duvelisib, CAR T-cells
- Medical subject headings
- Lymphoma, Non-Hodgkin, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuvelisibDrug
Patients should take duvelisib at approximately the same time every day, with or without food.
CAR T-cellsBiological
CAR T-cells will be given per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Dose Level 1: Duvelisib (15mg) | Experimental | * Patients will receive 15 mg of Duvelisib orally twice a day from Day -2 through Day 28 for 1 cycle
* CAR T-cells will be given per standard of care. Receives: Drug: Duvelisib; Biological: CAR T-cells |
| Dose Escalation Dose Level 2: Duvelisib (25mg) | Experimental | * Patients will receive 25 mg of Duvelisib orally twice a day from Day -2 through Day 28 for 1 cycle
* CAR T-cells will be given per standard of care. Receives: Drug: Duvelisib; Biological: CAR T-cells |
| Dose Expansion Cohort A: Duvelisib (25mg) | Experimental | * Patients in Cohort A will receive 25 mg (dose determined in dose escalation) duvelisib orally from Day -2 to Day 28 for 1 cycle.
* CAR T-cells will be given per standard of care. Receives: Drug: Duvelisib; Biological: CAR T-cells |
| Dose Expansion Cohort B: Duvelisib (25mg) | Experimental | * Patients in Cohort B will receive 25mg (dose determined in dose escalation) duvelisib orally from Day -2 to Day 180 as follows:
* Cycle 1 dosing begins on Day -2 and continues through Day 28 followed by 2 weeks off therapy
* Cycles 2-6 are 28 days long and consist of dosing on Days 1 through 14, with 2 weeks off therapy.
* CAR T-cells will be given per standard of care. Receives: Drug: Duvelisib; Biological: CAR T-cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity as measured by number of adverse events
Toxicity is graded using NCI CTCAE v 5.0
Measured: From start of treatment through 30 days after completion of duvelisib (up to day 60 for Cohort A and up to day 212 for Cohort B)
Secondary outcomes (14)
Cumulative incidence of cytokine release syndrome (CRS)
-Any and grade 3-4 per ASTCT criteria
Measured: By Day 28
Cumulative incidence of immune effector cell-associated neurotoxicity syndrome (ICANS)
-Any and grade 3-4 per ASCT criteria
Measured: By Day 28
Number of participants who receive anti-IL-6 agents for treatment of cytokine release syndrome (CRS)
Measured: Through completion of follow-up (estimated to be 6 months)
Number of participants who receive steroids for treatment of cytokine release syndrome (CRS)
Measured: Through completion of follow-up (estimated to be 6 months)
Number of participants with complete response (CR)
Measured: At 1 month
Number of participants with complete response (CR)
Measured: At 3 months
Number of participants with complete response (CR)
Measured: At 6 months
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Measured: At 1 month
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Measured: At 3 months
Best overall response rate
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
Measured: At 6 months
Progression-free survival (PFS)
Measured: Through completion of follow-up (estimated to be 5 years)
Overall survival (OS)
Measured: Through completion of follow-up (estimated to be 5 years)
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 90
Measured: Day 90
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 180
Measured: Day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2021
- Study start28 Feb 2022
- Primary completion6 Jan 2026
- Study completion22 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- SecuraBio, The Foundation for Barnes-Jewish Hospital
- Responsible party
- Sponsor
- Investigators
- Armin Ghobadi, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05044039
- Sponsor's protocol ID
- 202111018
- Status last verified
- Sep 2026
- First submitted
- 3 Sep 2021
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation and Dose Expansion Study of Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy
- ClinicalTrials.gov ID
- NCT05044039
- Acronym / sponsor ID
- 202111018
- Conditions
- Non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- SecuraBio, The Foundation for Barnes-Jewish Hospital
- Study start
- 28 Feb 2022 (actual)
- Primary completion
- 6 Jan 2026 (actual)
- Study completion
- 22 May 2030 (estimated)
- First posted
- 14 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While chimeric antigen receptor T-cell (CAR T-cell) therapy produces impressive response rates in heavily pre-treated patients, early loss of response remains a barrier. One potential mechanism of relapse is limited CAR T-cell persistence. Pre-clinical research shows that PI3K inhibition represents an intriguing mechanism for increasing CAR T-cell persistence that is easily reversible and CAR T-cell agnostic. The investigators hypothesize that PI3K inhibition with duvelisib would be safe, may provide effective prophylaxis against cytokine release syndrome (CRS), and may enhance the persistence and efficacy of CAR T-cells in the treatment of hematologic malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Dose Level 1: Duvelisib (15mg) | Experimental | Drug: Duvelisib, Biological: CAR T-cells* Patients will receive 15 mg of Duvelisib orally twice a day from Day -2 through Day 28 for 1 cycle * CAR T-cells will be given per standard of care. |
| Dose Escalation Dose Level 2: Duvelisib (25mg) | Experimental | Drug: Duvelisib, Biological: CAR T-cells* Patients will receive 25 mg of Duvelisib orally twice a day from Day -2 through Day 28 for 1 cycle * CAR T-cells will be given per standard of care. |
| Dose Expansion Cohort A: Duvelisib (25mg) | Experimental | Drug: Duvelisib, Biological: CAR T-cells* Patients in Cohort A will receive 25 mg (dose determined in dose escalation) duvelisib orally from Day -2 to Day 28 for 1 cycle. * CAR T-cells will be given per standard of care. |
| Dose Expansion Cohort B: Duvelisib (25mg) | Experimental | Drug: Duvelisib, Biological: CAR T-cells* Patients in Cohort B will receive 25mg (dose determined in dose escalation) duvelisib orally from Day -2 to Day 180 as follows: * Cycle 1 dosing begins on Day -2 and continues through Day 28 followed by 2 weeks off therapy * Cycles 2-6 are 28 days long and consist of dosing on Days 1 through 14, with 2 weeks off therapy. * CAR T-cells will be given per standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Meets FDA-approved criteria for treatment of non-Hodgkin lymphoma (NHL) with axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), lisocabtagene maraleucel (Breyanzi) or brexucabtagene autoleucel (Tecartus). Subjects receiving breuxacabtagene autoleucel for treatment of B-cell acute lymphoblastic leukemia (ALL) are not eligible.
- At least 18 years of age.
- The effects of duvelisib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for at least 3 months after the last dose of duvelisib, as well as conform to institutional CAR T-cell guidelines. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for at least 3 months after the last dose of duvelisib.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Key exclusion criteria (20 listed)
- Receiving axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, or brexucabtagene autoleucel for the treatment of B-cell acute lymphoblastic leukemia.
- Known allergy or intolerance to duvelisib or another PI3K inhibitor. Previous treatment with duvelisib or other PI3K inhibitor is permitted unless therapy was discontinued due to toxicity or intolerance of therapy.
- Receiving therapy with a strong CYP3A inducer or inhibitor that cannot be discontinued during duvelisib therapy. Subjects receiving a strong CYP3A inducer or inhibitor at screening are eligible to participate if the drug can be discontinued the longest of the following time periods prior to initiation of duvelisib: 7 days (for strong CYP3A inhibitors), 14 days (for strong CYP3A inducers) or 4-5 half-lives (either inducer or inhibitor).
- Active CNS involvement by hematologic malignancy under treatment
- Evidence of uncontrolled infection of any origin (viral, bacterial, or fungal)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DuvelisibPatients should take duvelisib at approximately the same time every day, with or without food. | Drug | Dose Escalation Dose Level 1: Duvelisib (15mg), Dose Escalation Dose Level 2: Duvelisib (25mg), Dose Expansion Cohort A: Duvelisib (25mg), Dose Expansion Cohort B: Duvelisib (25mg) |
| CAR T-cellsCAR T-cells will be given per standard of care. | Biological | Dose Escalation Dose Level 1: Duvelisib (15mg), Dose Escalation Dose Level 2: Duvelisib (25mg), Dose Expansion Cohort A: Duvelisib (25mg), Dose Expansion Cohort B: Duvelisib (25mg) |
Primary outcome
Toxicity as measured by number of adverse events
Time frame: From start of treatment through 30 days after completion of duvelisib (up to day 60 for Cohort A and up to day 212 for Cohort B)
Toxicity is graded using NCI CTCAE v 5.0
14 secondary outcomes
Cumulative incidence of cytokine release syndrome (CRS)
Time frame: By Day 28
Cumulative incidence of immune effector cell-associated neurotoxicity syndrome (ICANS)
Time frame: By Day 28
Number of participants who receive anti-IL-6 agents for treatment of cytokine release syndrome (CRS)
Time frame: Through completion of follow-up (estimated to be 6 months)
Number of participants who receive steroids for treatment of cytokine release syndrome (CRS)
Time frame: Through completion of follow-up (estimated to be 6 months)
Number of participants with complete response (CR)
Time frame: At 1 month
Number of participants with complete response (CR)
Time frame: At 3 months
Number of participants with complete response (CR)
Time frame: At 6 months
Best overall response rate
Time frame: At 1 month
Best overall response rate
Time frame: At 3 months
Best overall response rate
Time frame: At 6 months
Progression-free survival (PFS)
Time frame: Through completion of follow-up (estimated to be 5 years)
Overall survival (OS)
Time frame: Through completion of follow-up (estimated to be 5 years)
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 90
Time frame: Day 90
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 180
Time frame: Day 180
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Armin Ghobadi, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Duvelisib and CAR T-cells in people with Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia, run by Washington University School of Medicine at 1 site 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 4 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity as measured by number of adverse events (time frame: From start of treatment through 30 days after completion of duvelisib (up to day 60 for Cohort A and up to day 212 for Cohort B)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Sep 2026.