Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy

NCT05044039 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021110185R35CA210084
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (1)

• Toxicity as measured by number of adverse events

  Toxicity is graded using NCI CTCAE v 5.0

  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)

  By Day 28

• Cumulative incidence of immune effector cell-associated neurotoxicity syndrome (ICANS)

  By Day 28

• Number of participants who receive anti-IL-6 agents for treatment of cytokine release syndrome (CRS)

  Through completion of follow-up (estimated to be 6 months)

• Number of participants who receive steroids for treatment of cytokine release syndrome (CRS)

  Through completion of follow-up (estimated to be 6 months)

• Number of participants with complete response (CR)

  At 1 month

Study Arms (3)

Dose Escalation Stage: Duvelisib

EXPERIMENTAL

* Duvelisib is an oral medication taken on a once or twice daily basis on all dosing days. Doses being explored in this study are 15 mg BID (starting dose), 25 mg BID, and 15 mg QD. In the dose escalation stage, patients will receive duvelisib from Day -2 through Day 28. * CAR T-cells will be given per standard of care.

Drug: Duvelisib

Cohort A Dose Expansion Stage: Duvelisib

EXPERIMENTAL

* Patients in Cohort A will receive duvelisib from Day -2 to Day 28. The dose that will be given will be determined in the dose escalation stage (the maximum tolerated dose). * CAR T-cells will be given per standard of care.

Drug: Duvelisib

Cohort B Dose Expansion Stage: Duvelisib

EXPERIMENTAL

* Patients in Cohort B will receive duvelisib 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.

Drug: Duvelisib

Interventions

Duvelisib DRUG

Patients should take duvelisib at approximately the same time every day, with or without food.

Cohort A Dose Expansion Stage: Duvelisib; Cohort B Dose Expansion Stage: Duvelisib; Dose Escalation Stage: Duvelisib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• SecuraBio: collaborator
• The Foundation for Barnes-Jewish Hospital: collaborator
• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

duvelisib

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Armin Ghobadi, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2021
• First Posted: September 14, 2021
• Study Start: February 28, 2022
• Primary Completion: January 6, 2026
• Study Completion (Estimated): May 22, 2030
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)