What is the mechanism of action of this treatment?

The most common treatments for Mycosis Fungoides and Sezary Syndrome include enzyme inhibitors like Duvelisib and immune checkpoint inhibitors like Nivolumab. Duvelisib works by inhibiting specific enzymes necessary for tumor cell growth, thereby preventing their proliferation. Nivolumab, on the other hand, activates the immune system by blocking the PD-1 pathway, enabling immune cells to better recognize and attack cancer cells. These targeted approaches are significant for patients as they aim to halt tumor growth and enhance the body's immune response, potentially improving clinical outcomes.

What side effects are associated with this type of intervention?

Common treatments for Mycosis Fungoides and Sezary Syndrome that are similar to Duvelisib (an enzyme inhibitor) and Nivolumab (an immune checkpoint inhibitor) include other enzyme inhibitors and immune checkpoint inhibitors. Known side effects of enzyme inhibitors like Duvelisib can include diarrhea, fatigue, nausea, and infections due to immunosuppression. Immune checkpoint inhibitors like Nivolumab can cause immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. These treatments require careful monitoring to manage and mitigate these potential side effects.

What prior FDA approvals exist?

Prior FDA approvals for the treatment of Mycosis Fungoides and Sezary Syndrome include drugs like vorinostat and romidepsin, which are histone deacetylase inhibitors, and mogamulizumab, a monoclonal antibody targeting CCR4. These treatments, like duvelisib and nivolumab, aim to inhibit specific pathways or activate the immune system to combat the cancer cells.

What other types of research exist?

Promising novel alternatives for Mycosis Fungoides and Sezary Syndrome patients include: 1) Mogamulizumab, a monoclonal antibody targeting CCR4, which has shown efficacy in cutaneous T-cell lymphomas. 2) Brentuximab vedotin, an antibody-drug conjugate targeting CD30, used in relapsed or refractory cases. 3) Pembrolizumab, another PD-1 inhibitor, which may offer benefits similar to Nivolumab. 4) Chimeric Antigen Receptor (CAR) T-cell therapy, which is an emerging treatment showing potential in various lymphomas.

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PI3K Inhibitor

Duvelisib + Nivolumab for Skin Cancer

Phase 1

Recruiting

Led By Neha Mehta-Shah

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 50%)

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

Must not have

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

Prior therapy with a PI3K inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests duvelisib and nivolumab in patients with advanced mycosis fungoides and Sezary syndrome. Duvelisib blocks cancer cell growth, and nivolumab boosts the immune system to fight cancer. The goal is to find the best dose and see if this combination works better than current treatments.

Who is the study for?

Adults over 18 with stage IIB-IVB mycosis fungoides or Sezary syndrome who've had prior systemic therapy can join this trial. They must have certain levels of blood cells, kidney and liver function, and controlled brain metastases if present. Heart disease patients need a specific risk assessment. Participants must use effective contraception and not be pregnant or breastfeeding.

What is being tested?

The trial is testing the combination of duvelisib (which blocks enzymes for cell growth) with nivolumab (an immunotherapy that helps the immune system attack cancer). It aims to find the best dose, benefits, and side effects compared to usual treatments for these skin cancers.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as inflammation in various organs, potential impact on blood counts leading to increased infection risk, fatigue, digestive issues, and possibly others not yet known due to limited data.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself but might not be able to do heavy physical work.

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I am 18 years old or older.

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I have confirmed MF or SS skin lymphoma at stage IIB to IVB with measurable disease.

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I have received at least one round of treatment for my condition.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have an active or history of severe autoimmune disease.

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I have been treated with a PI3K inhibitor before.

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I have previously been treated with drugs that boost the immune system.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years post-treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose or recommended phase II dose (RP2D)

Secondary study objectives

Complete response rate (CRR)

Disease control rate (DCR)

Duration of response (DOR) for responding patients

+5 more

Other study objectives

Change in the immune composition

Side effects data

From 2021 Phase 3 trial • 319 Patients • NCT02004522

50%

Diarrhoea

34%

Neutropenia

29%

Pyrexia

25%

Anaemia

24%

Nausea

23%

Cough

17%

Thrombocytopenia

17%

Constipation

16%

Fatigue

16%

Pneumonia

15%

Vomiting

15%

Decreased appetite

14%

Upper respiratory tract infection

13%

Asthenia

13%

Colitis

13%

Weight decreased

13%

Bronchitis

11%

Abdominal pain

11%

Rash

10%

Hypokalaemia

10%

Oedema peripheral

Aspartate aminotransferase increased

Dyspnoea

Alanine aminotransferase increased

Back pain

Dizziness

Headache

Hypertension

Nasopharyngitis

Arthralgia

Pruritus

Hyperkalaemia

Respiratory tract infection

Rash maculo-papular

Febrile neutropenia

Rhinorrhoea

Dyspepsia

Pain in extremity

Abdominal pain upper

Dehydration

Insomnia

Productive cough

Dry mouth

Muscle spasms

Paraesthesia

Pneumonitis

Renal failure acute

Toxic skin eruption

Hypotension

General physical health deterioration

Gastroenteritis

Gastritis

Pneumonia pseudomonas aeruginosa

Pancytopenia

Cardiac failure

Sepsis

Pneumocystis jirovecii pneumonia

Pneumonia pneumococcal

Pulmonary embolism

Respiratory failure

Pneumonia aspiration

Pneumonia klebsiella

Interstitial lung disease

Urinary tract infection

Pneumonia staphylococcal

Pleural haemorrhage

Streptococcal sepsis

Skin infection

Rash erythematous

Accidental overdose

Fungal oesophagitis

Upper gastrointestinal haemorrhage

Proctitis

Enterocolitis

Mental impairment

Intestinal adenocarcinoma

Deep vein thrombosis

Haemolytic anaemia

Atrial fibrillation

Cardiac failure congestive

Myocardial infarction

Pericarditis

Death

Mucosal inflammation

Multi-organ failure

Sudden death

Transitional cell carcinoma

Bronchiolitis

Bronchitis viral

Bronchopneumonia

Cytomegalovirus colitis

Pneumonia escherichia

Pneumonia mycoplasmal

Septic shock

Streptococcal bacteraemia

Subdural haematoma

Lipase increased

Nephrolithiasis

Renal colic

Renal failure

Renal failure chronic

Lung disorder

Ventricular tachycardia

Colitis ischaemic

Enteritis

Pancreatitis acute

Ileal ulcer

Aspergillus infection

Bronchopulmonary aspergillosis

Campylobacter gastroenteritis

Clostridium difficile colitis

Fungal infection

Influenza

Pseudomonal sepsis

Lower respiratory tract infection

Pneumonia bacterial

Enterococcal infection

Enterococcal sepsis

Escherichia sepsis

Escherichia urinary tract infection

Gastroenteritis viral

Haemophilus infection

Infection

Infusion site cellulitis

Lobar pneumonia

Lower respiratory tract infection viral

Lung infection

Pneumonia respiratory syncytial viral

Pneumonia streptococcal

Pseudomonas bronchitis

Wound infection staphylococcal

Cervical vertebral fracture

Femur fracture

Traumatic haematoma

Malnutrition

Hyponatraemia

Tumour lysis syndrome

Arthritis

Bone pain

Malignant melanoma

Brain stem haemorrhage

Dementia

Acute respiratory distress syndrome

Acute respiratory failure

Chronic obstructive pulmonary disease

Dermatitis exfoliative

Thrombosis

Infusion related reaction

Neuroendocrine tumour

Pleural effusion

Mallory-Weiss syndrome

Diverticulitis

Pyelonephritis

Haemorrhagic stroke

Dermatitis allergic

Respiratory tract infection bacterial

Splenic rupture

Neuroendocrine carcinoma of the skin

100%

80%

60%

40%

20%

Study treatment Arm

Duvelisib

Ofatumumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (duvelisib, nivolumab)Experimental Treatment6 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Computed Tomography

2017

Completed Phase 2

~2740

Positron Emission Tomography

2011

Completed Phase 2

~2200

Duvelisib

2016

Completed Phase 3

~760

Nivolumab

2014

Completed Phase 3

~5220

Punch Biopsy

2017

N/A

~40

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Mycosis Fungoides and Sezary Syndrome include enzyme inhibitors like Duvelisib and immune checkpoint inhibitors like Nivolumab. Duvelisib works by inhibiting specific enzymes necessary for tumor cell growth, thereby preventing their proliferation. Nivolumab, on the other hand, activates the immune system by blocking the PD-1 pathway, enabling immune cells to better recognize and attack cancer cells. These targeted approaches are significant for patients as they aim to halt tumor growth and enhance the body's immune response, potentially improving clinical outcomes.

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