- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05044039
Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy
March 12, 2024 updated by: Washington University School of Medicine
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Estimated)
43
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Armin Ghobadi, M.D.
- Phone Number: 314-454-8304
- Email: arminghobadi@wustl.edu
Study Locations
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Sub-Investigator:
- John F DiPersio, M.D., Ph.D.
-
Sub-Investigator:
- Feng Gao, Ph.D.
-
Principal Investigator:
- Armin Ghobadi, M.D.
-
Contact:
- Armin Ghobadi, M.D.
- Phone Number: 314-454-8304
- Email: arminghobadi@wustl.edu
-
Sub-Investigator:
- Michael Slade, M.D.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
- 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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: Cohort A Dose Expansion Stage: Duvelisib
|
Patients should take duvelisib at approximately the same time every day, with or without food.
|
Experimental: Dose Escalation Stage: Duvelisib
|
Patients should take duvelisib at approximately the same time every day, with or without food.
|
Experimental: Cohort B Dose Expansion Stage: Duvelisib
|
Patients should take duvelisib at approximately the same time every day, with or without food.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity as measured by number of adverse events
Time Frame: From start of treatment through 30 days after completion of treatment (up to day 60 for Cohort A and up to day 212 for Cohort B)
|
Toxicity is graded using NCI CTCAE v 5.0
|
From start of treatment through 30 days after completion of treatment (up to day 60 for Cohort A and up to day 212 for Cohort B)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative incidence of cytokine release syndrome (CRS)
Time Frame: By Day 28
|
-Any and grade 3-4 per ASTCT criteria
|
By Day 28
|
Cumulative incidence of immune effector cell-associated neurotoxicity syndrome (ICANS)
Time Frame: By Day 28
|
-Any and grade 3-4 per ASCT criteria
|
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)
|
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)
|
Through completion of follow-up (estimated to be 6 months)
|
|
Best overall response rate
Time Frame: At 1 month
|
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
|
At 1 month
|
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 90
Time Frame: Day 90
|
Day 90
|
|
Proportion of participants with partial response (PR) on Day 30 with improved response on Day 180
Time Frame: Day 180
|
Day 180
|
|
Progression-free survival (PFS)
Time Frame: Through completion of follow-up (estimated to be 5 years)
|
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)
|
Through completion of follow-up (estimated to be 5 years)
|
|
Number of participants with complete response (CR)
Time Frame: At 1 month
|
At 1 month
|
|
Number of participants with complete response (CR)
Time Frame: At 3 months
|
At 3 months
|
|
Number of participants with complete response (CR)
Time Frame: At 6 months
|
At 6 months
|
|
Best overall response rate
Time Frame: At 3 months
|
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
|
At 3 months
|
Best overall response rate
Time Frame: At 6 months
|
-Defined as proportion of subjects with complete response (CR) or partial response (PR) by Lugano criteria
|
At 6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Armin Ghobadi, M.D., Washington University School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 28, 2022
Primary Completion (Estimated)
December 31, 2025
Study Completion (Estimated)
May 31, 2030
Study Registration Dates
First Submitted
September 3, 2021
First Submitted That Met QC Criteria
September 3, 2021
First Posted (Actual)
September 14, 2021
Study Record Updates
Last Update Posted (Actual)
March 13, 2024
Last Update Submitted That Met QC Criteria
March 12, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 202111018
- 5R35CA210084 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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.
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