What side effects are associated with this type of intervention?

Common treatments for B-Cell Lymphoma, including PI3K inhibitors like Duvelisib, often have side effects such as diarrhea, neutropenia, nausea, fatigue, and infections. Other treatments, such as chemotherapy and immunotherapy, can cause additional side effects like skin reactions, endocrine events, pneumonia, anemia, and febrile neutropenia. It's important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for B-Cell Lymphoma that are similar to Duvelisib, a PI3K inhibitor. Idelalisib, another PI3K inhibitor, has been approved for relapsed chronic lymphocytic leukemia (CLL) and follicular B-cell non-Hodgkin lymphoma. Additionally, other targeted therapies such as ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, and venetoclax, a BCL-2 inhibitor, have also been approved for various forms of B-Cell Lymphoma, including CLL and mantle cell lymphoma. These approvals highlight the ongoing development and validation of targeted therapies in the treatment of B-Cell Lymphomas.

What other types of research exist?

Promising alternatives to Duvelisib for B-Cell Lymphoma patients include: 1) CAR-T cell therapies, which involve modifying a patient's T cells to target lymphoma cells; 2) BTK inhibitors like Ibrutinib and Acalabrutinib, which block B-cell receptor signaling; 3) CD19-targeted therapies such as Tafasitamab in combination with Lenalidomide; and 4) Bispecific T-cell engagers (BiTEs) like Blinatumomab, which direct T cells to attack lymphoma cells. These therapies have shown significant efficacy in clinical trials and are expected to be important treatment options in 2024.

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PI3K Inhibitor

Duvelisib for Diffuse Large B-Cell Lymphoma

Q: What is the mechanism of action of this treatment?

The most common treatments for B-Cell Lymphoma include PI3K inhibitors like Duvelisib, which block the PI3K pathway crucial for cell growth and survival, thereby inducing cancer cell death. Monoclonal antibodies such as rituximab target the CD20 antigen on B-cells, marking them for destruction by the immune system. Combination therapies, like bendamustine plus rituximab, combine the DNA-damaging effects of chemotherapy with the targeted action of monoclonal antibodies, enhancing overall efficacy. These mechanisms are vital for B-Cell Lymphoma patients as they offer targeted, effective treatment options that can improve response rates and potentially prolong survival.

Phase < 1

Recruiting

Led By Edmund K Waller, MD, PhD

Research Sponsored by Emory University

Eligibility Criteria Checklist

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

Must have

Patients must have a biopsy proven diagnosis of relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

Sexually active males must use a condom during intercourse from enrollment into this study until at least 12 months after tisagenlecleucel infusion and until CAR-T cells are no longer present by qPCR on two consecutive tests (qPCR tests will be available upon request). A condom is required of all sexually active male patients to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner

Must not have

Patients with ongoing treatment for systemic bacterial, fungal or viral infection

Previous CD 19 directed therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 3 months following car-t cell infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if a new treatment can improve immune cells in patients with hard-to-treat lymphoma before using these cells for a special cancer treatment. The goal is to make the immune cells stronger and more effective against cancer.

Who is the study for?

This trial is for adults with relapsed/refractory diffuse large B-cell lymphoma. Participants must be in good physical condition (ECOG < 2), have normal organ function, and not be pregnant or breastfeeding. They should agree to use effective contraception and not donate blood or organs during the study. People with CNS lymphoma involvement, autoimmune diseases, active infections, recent immunosuppressive therapy, or prior CD19 directed therapy are excluded.

What is being tested?

The DEEP T CELLS Study is testing whether taking duvelisib before manufacturing CAR-T cells can improve the immune profiles of T cells in patients with difficult-to-treat diffuse large B-cell lymphoma. Duvelisib is an oral drug that may make T cells more efficient for later CAR-T cell treatment.

What are the potential side effects?

Duvelisib might cause diarrhea, liver enzyme changes, fatigue, fever, coughing and other respiratory issues. It could also increase the risk of infections due to its effect on the immune system.

Eligibility Criteria

Inclusion Criteria

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

Select...

My biopsy shows I have relapsed or refractory DLBCL.

Select...

I am a man who will use a condom for 12 months after treatment and until tests confirm the treatment is not in my system.

Select...

I have been using a reliable birth control method for at least 3 months.

Select...

I can do all my daily activities without help.

Select...

I agree not to donate blood or organs while on treatment and for a year after.

Exclusion Criteria

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

Select...

I am currently being treated for a serious infection.

Select...

I have had treatment targeting CD19 before.

Select...

I am not pregnant or breastfeeding.

Select...

My cancer is a type of lymphoma that affects the brain.

Select...

My lymphoma has spread to my brain or spinal cord.

Select...

I have been diagnosed with systemic lupus erythematosus.

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I have been diagnosed with Grave's disease.

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I have rheumatoid arthritis.

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I am currently taking immunosuppressive medication, including steroids.

Select...

I do not have active HIV, Hepatitis B, or Hepatitis C infections.

Select...

I cannot take preventive treatments for pneumocystis or herpes viruses.

Select...

I have a history of chronic liver disease.

Select...

I have an inflammatory bowel disease like Crohn's, ulcerative colitis, or celiac.

Select...

I have myasthenia gravis.

Select...

I have been diagnosed with Wegener's syndrome.

Select...

I have been treated with a PI3K inhibitor before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 3 months following car-t cell infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 3 months following car-t cell infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 3 months following car-t cell infusion for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Fold-change increase in CD27/CD28 double positive T cells

Secondary study objectives

Change in proportion of CD27/28 double positive T cells and CD4/8 double negative T cells

Frequency of intensive care unit (ICU) transfers due to cytokine release syndrome (CRS) and/or neurotoxicity

Incidence of grade III-IV adverse events

+3 more

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)Experimental Treatment2 Interventions

Patients receive duvelisib PO BID for 2 weeks prior to collection of CAR-T cells in the absence of disease progression or unacceptable toxicity. Patients then receive tisagenlecleucel via infusion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tisagenlecleucel

2019

Completed Phase 2

~370

Duvelisib

2016

Completed Phase 3

~760

0 / 21Eligibility 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 B-Cell Lymphoma include PI3K inhibitors like Duvelisib, which block the PI3K pathway crucial for cell growth and survival, thereby inducing cancer cell death. Monoclonal antibodies such as rituximab target the CD20 antigen on B-cells, marking them for destruction by the immune system. Combination therapies, like bendamustine plus rituximab, combine the DNA-damaging effects of chemotherapy with the targeted action of monoclonal antibodies, enhancing overall efficacy. These mechanisms are vital for B-Cell Lymphoma patients as they offer targeted, effective treatment options that can improve response rates and potentially prolong survival.

The treatment of Burkitt lymphoma in adults.