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


About this study

This phase I trial identifies the best dose, possible benefits, and/or side effects of duvelisib in combination with nivolumab in treating patients with stage IIB-IVB mycosis fungoides and Sezary syndrome. Duvelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving duvelisib in combination with nivolumab may work better than giving each of these drugs individually, or treating with the usual approach in patients with mycosis fungoides and Sezary syndrome.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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 treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression

- 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 investigational
drug. 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. 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

- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial

Exclusion Criteria:

- Prior therapy with a PI3K inhibitor

- Prior therapy with nivolumab or other agents targeting T-cell co-stimulation or
checkpoint pathways

- Patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids, should be excluded. These include but are not
limited to patients with a history of immune related neurologic disease, multiple
sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia
gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE),
connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's,
ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
excluded because of the risk of recurrence or exacerbation of disease. Patients with
vitiligo, endocrine deficiencies including thyroiditis managed with replacement
hormones including physiologic corticosteroids are eligible. Patients with rheumatoid
arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with
topical medication and patients with positive serology, such as antinuclear antibodies
(ANA), anti-thyroid antibodies should be evaluated for the presence of target organ
involvement and potential need for systemic treatment but should otherwise be eligible

- Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis not requiring systemic treatment, or conditions not expected to
recur in the absence of an external trigger (precipitating event)

- Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 7 days of study drug administration. Inhaled or
topical steroids, steroids for physiologic or adrenal replacement doses =< 10 mg daily
prednisone equivalents are permitted in the absence of active autoimmune disease.
Patients are permitted to use topical, ocular, intra-articular, intranasal, and
inhalational corticosteroids (with minimal systemic absorption). A brief course of
corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of
non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by
contact allergen) is permitted

- History of tuberculosis treatment within the 2 years prior to enrollment

- Ongoing treatment with other immunosuppressive agent including, but not limited to,
methotrexate, azathioprine, anti-tumor necrosis factor (TNF) agents, etc. with the
exception of steroids

- Administration of a live or live attenuated vaccine within 6 weeks of initiation of
study therapy

- Ongoing treatment with systemic steroids at dose equivalent to greater than prednisone
10 mg daily or other immunosuppressive medication within 7 days of initiation of study

- Inhaled steroids will be permitted

- Topical steroids for cutaneous manifestations of MF/SS will be permitted below:

- Continued use of select concomitant topical steroids is permitted if the
patient has remained clinically stable for at least 4 weeks.

- Patients who are on low or moderate potency topical corticosteroids may
participate if they are on a stable dose for at least 4 weeks before
enrollment. Local injections of corticosteroids are acceptable; all
corticosteroids will be reported as concomitant medications.

- Patients prescribed prednisone 10 mg PO daily or less (or equivalent) will not be

- Concomitant use of another systemic therapy for MF/SS. Patients must have the
following minimum wash-out from previous treatments:

- At least 8 weeks for low-dose (12 Gy or less) total skin electron beam therapy

- At least 4 weeks for systemic cytotoxic anticancer agents or for tumor-targeting
monoclonal antibodies (mAbs), with the exception of alemtuzumab, for which the
washout is at least 16 weeks

- At least 2 weeks or 5 half-lives for systemic retinoids, interferons, vorinostat,
romidepsin, and denileukin diftitox, or anticancer investigational agents that
are not defined as immunotherapy

- At least 2 weeks for local radiation therapy

- At least 1 week for topical retinoids, nitrogen mustard, or imiquimod

- Concomitant malignancy requiring active systemic therapy, excluding adjuvant endocrine
therapy with the following exceptions:

- Patients with non-melanoma skin cancer or carcinoma in situ of the cervix will
not be excluded

- Adjuvant or maintenance therapy to reduce the risk of recurrence of another
malignancy (excluding cutaneous T-cell lymphoma) is permissible after discussion
with the Washington University principal investigator

- Subjects with previous malignancies are eligible if disease-free for > 2 years

- History of solid organ transplantation or allogeneic bone marrow transplantation

- Uncontrolled infection requiring systemic antimicrobials: Patients on antibacterial,
antifungal, and antiviral prophylaxis will not be excluded if all other exclusion /
inclusion criteria are met

- 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

- 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

- 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

- Pregnant women are excluded from this study because nivolumab has 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, breastfeeding should be discontinued if the mother is treated with
nivolumab. 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

Eligibility last updated 8/8/22. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Nabila Bennani, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Muhamad Alhaj Moustafa, M.D., M.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Allison Rosenthal, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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