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

NCT04652960 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2020-1164110347UM1CA186689
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v8; Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8; Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose or recommended phase II dose (RP2D)

  If one dose-limiting toxicity (DLT) is seen in the first three patients treated at a given dose level, then three additional patients will be evaluated at that same dose level. If DLTs are present at \< 2 of 6 patients, the next dose level will be explored. If 3 patients are treated at the maximal dose level without DLT, three more patients will be enrolled to that dose level to evaluate for DLT. If \< 2/6 DLTs are seen at that dose level, it will be deemed the RP2D.

  Through completion of 3 cycles (each cycle is 28 days)

• Incidence of adverse events

  For 30 days after last dose of study treatment or until the initiation of alternative treatment, whichever comes first. If removed for an adverse event, the adverse event causing removal will be followed until resolution or stabilization

Secondary Outcomes (8)

• Overall response rate (ORR)

  At 4 months

• Complete response rate (CRR)

  Up to 2 years post-treatment

• Overall response rate (ORR) for all treated patients

  Up to 2 years post-treatment

• Disease control rate (DCR)

  At 4 months

• Duration of response (DOR) for responding patients

  From the first documentation of response to the first documentation of progressive disease (PD) or death due to any cause, assessed up to 2 years post-treatment

Other Outcomes (1)

• Change in the immune composition

  Before the start of treatment, on treatment, at end of treatment, and at the time of flare, up to 2 years post-treatment

Study Arms (1)

Treatment (duvelisib, nivolumab)

EXPERIMENTAL

Patients receive duvelisib PO QD or BID on days 1-28 or days 1-14 and nivolumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo PET-CT or CT scan at baseline. Patients also undergo punch biopsy and collection of blood samples throughout the trial.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Duvelisib; Biological: Nivolumab; Procedure: Positron Emission Tomography; Procedure: Punch Biopsy

Interventions

Punch Biopsy PROCEDURE

Undergo punch biopsies

Also known as: BIOPSY, PUNCH, Punch Biopsy of Skin

Treatment (duvelisib, nivolumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (duvelisib, nivolumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (duvelisib, nivolumab)

Duvelisib DRUG

Given PO

Also known as: 8-Chloro-2-phenyl-3-((1S)-1-(7H-purin-6-ylamino)ethyl)isoquinolin-1(2H)-one, Copiktra, INK-1197, IPI 145, IPI-145, IPI145

Treatment (duvelisib, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (duvelisib, nivolumab)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (duvelisib, nivolumab)

Eligibility Criteria

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

You may qualify if:

• 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 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

You may not qualify if:

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Mycosis Fungoides; Sezary Syndrome

Interventions

Specimen Handling; duvelisib; Nivolumab; Magnetic Resonance Spectroscopy; Biopsy

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Spectrum Analysis; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Neha Mehta-Shah

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 4, 2020
• Study Start: October 21, 2021
• Primary Completion (Estimated): December 3, 2026
• Study Completion (Estimated): December 3, 2026
• Last Updated: April 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (17)