Duvelisib Following Chimeric Antigen Receptor T-Cell Therapy

Inclusion Criteria:

• Meets FDA-approved criteria for treatment of non-Hodgkin lymphoma (NHL) withaxicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), lisocabtagenemaraleucel (Breyanzi) or brexucabtagene autoleucel (Tecartus). Subjects receivingbreuxacabtagene 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, forthe duration of study participation, and for at least 3 months after the last doseof duvelisib, as well as conform to institutional CAR T-cell guidelines. Should awoman become pregnant or suspect she is pregnant while participating in this study,she must inform her treating physician immediately. Men treated or enrolled on thisprotocol must also agree to use adequate contraception prior to the study, for theduration 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 informedconsent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Receiving axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, orbrexucabtagene autoleucel for the treatment of B-cell acute lymphoblastic leukemia.

• Known allergy or intolerance to duvelisib or another PI3K inhibitor. Previoustreatment with duvelisib or other PI3K inhibitor is permitted unless therapy wasdiscontinued due to toxicity or intolerance of therapy.

• Receiving therapy with a strong CYP3A inducer or inhibitor that cannot bediscontinued during duvelisib therapy. Subjects receiving a strong CYP3A inducer orinhibitor at screening are eligible to participate if the drug can be discontinuedthe 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 treatmentwithin the two years prior to study enrollment

• Known HIV infection, untreated hepatitis C or hepatitis B infection. Untreatedhepatitis 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 todiagnosis of hematologic malignancy under treatment

• Clinically significant pulmonary disease, defined as grade 2 or greater dyspnea orgrade 2 or greater hypoxia

• Clinically significant cardiac disease, defined as unstable angina, acute myocardialinfarction in the last 6 months, and NYHA class II or IV heart failure. Subjectswith unstable arrhythmias that are not stable with medical management in 2 weeksprior 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 orMeulengracht's syndrome). Subjects with a history of chronic liver disease, previousveno-occlusive disease, active alcohol abuse or history of alcohol abuse within thepast 6 months are also excluded.

• Clinically significant renal disease, defined as calculated or measured creatinineclearance < 50 mL/min

• Currently breastfeeding or pregnant. Women of childbearing potential must have anegative pregnancy test within 7 days of study entry.

• Inability to swallow and retain oral medication or prior surgery or GI dysfunctionthat may affect drug absorption (i.e. gastric bypass surgery, gastrectomy)

• Receipt of a prior investigational agent within 4 weeks before Day -3 or currentlyreceiving 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 fullparticipation in the study, including administration of medication, attendance ofstudy visits, elevated risk of complications or interference with interpretation ofthe study data

• A history of other malignancy with the exception of malignancies for which alltreatment was completed at least 2 years before registration and the patient has noevidence of disease. Non-metastatic, non-melanoma skin cancers are not consideredexclusionary.