Inclusion Criteria:
- Patients must have a biopsy proven diagnosis of relapsed/refractory diffuse large
B-cell lymphoma (DLBCL)
- Eastern Cooperative Oncology Group (ECOG) < 2
- Serum creatinine (Cr) < 2.0 mg/dL
- Alanine aminotransferase (AST)/aspartate aminotransferase (ALT) < 2 x upper limit of
normal (ULN)
- Total bilirubin < 2.0 mg/dL
- Hemoglobin > 8 g/dL
- Platelet count > 50 K/mcl
- An absolute neutrophil count (ANC) > 1,000/mm^3
- An absolute lymphocyte count (ALC) > 300/mm^3
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy,
immunotherapy, or investigational therapy) for the treatment of their DLBCL >= 2 weeks
before the start of duvelisib. There is no limit on how many previous lines of
treatment a patient may have received
- The effects of duvelisib on the developing human fetus are unknown. For this reason,
women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy
test prior to starting therapy. WOCBP and men must agree to use highly effective
contraception (hormonal or barrier method of birth control; abstinence) from
enrollment into this study until at least 12 months after tisagenlecleucel infusion
and until CAR-T cells are no longer present by quantitative polymerase chain reaction
(qPCR) on two consecutive tests (qPCR tests will be available upon request). A woman
of childbearing potential (WOCBP) is a sexually mature woman who: 1) has not undergone
a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
for at least 24 consecutive months (i.e., has had menses at any time in the preceding
24 consecutive months. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree to use
highly effective contraception prior to the study, for the duration of study
participation, and 3 months after completion of duvelisib administration. WOCBP must
have a negative pregnancy test within 24 hours of leukapheresis, lymphodepletion (if
performed) and tisagenlecleucel infusion (if lymphodepletion not performed)
- The patient must be willing to comply with fertility requirements as below:
- Total abstinence (when this is in line with the usual practice and lifestyle of the
patient). Periodic abstinence (i.e, calendar, ovulation, post-ovulation methods) and
withdrawals are not acceptable forms of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without a
hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks
before taking study treatment. In case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow-up hormone assessment
- Male sterilization (at least 6 months prior to screening). For female patients on the
study, the vasectomized male partner should be the sole partner
- Use of oral (estrogen and progesterone), injected or implanted hormonal methods of
contraception, or placement of an intrauterine device (IUD) or intrauterine system
(IUS) or other forms of contraception that comparable efficacy (failure rate < 1%). In
case of oral contraception, the woman should be stable on the same pill for a minimum
of 3 months prior to enrollment on the study
- Sexually active males must use a condom during intercourse from enrollment into this
study until at least 12 months after tisagenlecleucel infusion and until CAR-T cells
are no longer present by qPCR on two consecutive tests (qPCR tests will be available
upon request). A condom is required of all sexually active male patients to prevent
them from fathering a child AND to prevent delivery of study treatment via seminal
fluid to their partner
- Female patients must be either postmenopausal, free from menses >= 2 years (yrs),
surgically sterilized, willing to use two adequate barrier methods of contraception to
prevent pregnancy or agree to abstain from heterosexual activity starting with
screening and for 5 months after last treatment in all patients
- Patients must agree not to donate blood, sperm/ova or any other organs while taking
protocol therapy and for at least 12 months after stopping treatment
- Willingness and ability of the patient to comply with scheduled visits, drug
administration plan, protocol specified laboratory tests, other study procedures and
study restrictions
- Evidence of personally signed informed consent indicating that the subject is aware of
the neoplastic nature of the disease and has been informed on the procedures to be
followed, the experimental nature of the therapy, alternative, potential risks and
discomforts, potential benefits and other pertinent aspects of study participation
Exclusion Criteria:
- Primary central nervous system lymphoma
- Patients with central nervous system (CNS) involvement of lymphoma
- History of autoimmune disease, including but not limited to:
- Inflammatory bowel diseases (Crohn's disease, ulcerative colitis, celiac disease)
- Systemic lupus erythematosus
- Grave's disease
- Myasthenia gravis
- Rheumatoid arthritis
- Wegner's syndrome
- Patients with history of drug reaction and eosinophilia systemic syndrome (DRESS) or
toxic epidermal necrolysis (TEN)
- History of human immunodeficiency virus (HIV), active Hepatitis C Infection or active
Hepatitis B infection as defined by:
- Patients with a positive hepatitis B surface antigen (HBsAg) or hepatitis C
antibody (HCV Ab) will be excluded
- Patients with a positive hepatitis B core antibody (HBcAb) must have negative
hepatitis B virus (HBV) deoxyribonucleic acid (DNA) to be eligible and must be
periodically monitored for HBV reactivation by institutional guidelines
- Patients with active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection
(i.e., subjects with detectable viral load)
- Patients with ongoing treatment for systemic bacterial, fungal or viral infection
- Patients with history of immune or drug mediated colitis, hepatitis or pneumonitis
- Patients with previous treatment with a PI3K inhibitor
- Patients currently on immunosuppressive therapy, including steroids
- Previous CD 19 directed therapy
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 2 weeks earlier
(i.e., have residual toxicities > grade 1)
- Patients receiving any other investigational drugs
- Pregnant women are excluded from this study because duvelisib is agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with duvelisib, breastfeeding should be discontinued if the mother is treated
with duvelisib and breastfeeding should not be resumed until at least 1 month after
last dose of duvelisib
- Patients with history of chronic liver disease or veno-occlusive disease
- Patients that are unable to receive prophylactic treatment for pneumocystis, herpes
simplex virus (HSV), or herpes zoster "(VZV) at screening
- Patients with history of tuberculosis treatment within the 2 years prior to
randomization
- Patients with prior surgery or gastrointestinal dysfunction that may affect drug
absorption (e.g., gastric bypass surgery, gastrectomy). Subjects with clinically
significant medical condition of malabsorption, inflammatory bowel disease, chronic
conditions which manifest with diarrhea, refractory nausea, vomiting or any other
condition that will interfere significantly with drug absorption
- Concurrent administration of medications or foods that are strong inhibitors or
inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start
of study intervention
- Administration of a live or live attenuated vaccine within 6 weeks of randomization
