Duvelisib and Nivolumab for the Treatment of Stage IIB-IVB Mycosis Fungoides and Sezary Syndrome

Inclusion Criteria

• •Patients must have histologically or cytologically confirmed MF or SS, stages IIB to IVB with measurable disease and/or detectable blood involvement based on the Global Cutaneous Lymphoma Response Criteria
• •Patients must have had at least one line of prior systemic therapy
• •Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of duvelisib in combination with nivolumab in patients \< 18 years of age, children are excluded from this study
• •Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
• •Absolute neutrophil count \>= 1000/mcL
• •Platelets \> 75,000/mcL
• •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) or =\< 5 x institutional ULN if with history of Gilbert's syndrome
• •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
• •Creatinine =\< 2.0 x institutional ULN
• •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• •The effects of nivolumab and duvelisib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy for 5 months after the last dose of nivolumab and duvelisib. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 7 days prior to the start of nivolumab and duvelisib. Women must not be breastfeeding. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and duvelisib and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL
• •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 adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of administration of investigational agents on this study
• •Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
• •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• •History of solid organ transplantation or allogeneic bone marrow transplantation
• •Patients with active cytomegalovirus (CMV) (positive serology for anti-CMV IgM antibody and negative for anti-CMV IgG antibody or positive CMV PCR with clinical manifestations consistent with active CMV infection) and requiring therapy will be excluded from participation in the study. Carriers will be monitored per institutional guidelines
• •Patients should be excluded if they have known active hepatitis B (e.g. hepatitis B virus \[HBV\] surface antigen \[HBsAg\] reactive) or hepatitis C (e.g. hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
• •* Patients with chronic HBV or HCV are defined as patients with positive hepatitis B serology: Patients with a negative HBsAg and a positive hepatitis B core antibody (HBcAb) require an undetectable/negative hepatitis B deoxyribonucleic acid (DNA) test (e.g. polymerase chain reaction \[PCR\] test) to be enrolled, and will require prophylactic antiviral treatment initiated prior to the first dose of study drug, and continued until approximately 6 to 12 months after completion of study drug(s)
• •Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1), with the exception of alopecia and neuropathy
• •Patients who are receiving any other investigational agents
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to duvelisib or nivolumab
• •Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 are ineligible to start study therapy. Patients who are on strong inhibitors or inducers of CYP3A4 may start study therapy if discontinued 5 half lives before start of study therapy. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, congestive heart failure New York Heart Association (NYHA) grade \>= 3, unstable angina pectoris, and cardiac arrhythmia
• •Patients with psychiatric illness/social situations that would limit compliance with study requirements
• •Baseline QT interval corrected with Fridericia's method (QTcF) \> 500 ms
• •* Note: Criteria does not apply to subjects with a right or left bundle branch block
• •Pregnant women are excluded from this study because nivolumab and duvelisib have 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 nivolumab and duvelisib, breastfeeding should be discontinued if the mother is treated with nivolumab and duvelisib. These potential risks may also apply to other agents used in this study
• •Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study