NCT04652960

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

A Phase I Study With an Expansion Cohort of Duvelisib and Nivolumab in Mycosis Fungoides (MF) and Sézary Syndrome (SS)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine the recommended phase II dose (RP2D) or maximum tolerated dose (MTD) of the combination of duvelisib with nivolumab in patients with advanced mycosis fungoides/Sezary syndrome (MF/SS). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. Ia. To determine the overall response rate at four months to the combination of nivolumab and duvelisib. Ib. To determine the time to maximum response, best overall response rate, complete remission rate, and duration of response among responding patients. EXPLORATORY OBJECTIVES: I. To evaluate whether intra-patient changes in serum cytokines (soluble CD40L, TNF-beta, IL-17alpha, IL-15, CXCL13, IL-12p40) predict response to duvelisib in combination with nivolumab in cutaneous T-cell lymphoma (CTCL). II. To explore whether the combination of duvelisib and nivolumab changes the T-cell repertoire including T-cell receptor sequencing pre- and post- treatment with duvelisib and nivolumab in effort to better understand skin flare and other immunogenic reactions to this combination therapy. OUTLINE: This is a dose-escalation study of duvelisib in combination with fixed dose nivolumab followed by a dose-expansion study. Patients receive duvelisib orally (PO) once daily (QD) or twice daily (BID) on days 1-28 or days 1-14 and nivolumab intravenously (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 positron emission tomography (PET)-computed tomography (CT) or CT scan at baseline. Patients also undergo punch biopsy and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 6 months for 2 years.

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

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Duvelisib	Given PO
BIOLOGICAL	Nivolumab	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET
PROCEDURE	Punch Biopsy	Undergo punch biopsies

Timeline

• Start date: 2021-10-21
• Primary completion: 2026-12-03
• Completion: 2026-12-03
• First posted: 2020-12-04
• Last updated: 2026-04-13

Locations

17 sites across 1 country: United States

Regulatory

• FDA-regulated drug study