What is the mechanism of action of this treatment?

Hodgkin's Lymphoma treatments often target specific molecular pathways to inhibit tumor growth and survival. For example, Tazemetostat, an EZH2 inhibitor, works by blocking the EZH2 enzyme, which is involved in the methylation of histones and regulation of gene expression. This inhibition can prevent the proliferation of cancer cells and induce apoptosis. Targeted therapies like this are crucial for Hodgkin's Lymphoma patients as they offer a more precise treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for Hodgkin's Lymphoma include chemotherapy, radiation therapy, and targeted therapies. Chemotherapy regimens, such as ABVD (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine), can cause side effects like nausea, fatigue, hair loss, and increased risk of infections. Radiation therapy may lead to skin irritation, fatigue, and long-term risks such as secondary cancers. Targeted therapies, including newer agents like Tazemetostat (an EZH2 inhibitor), are being studied for their efficacy and safety. Known side effects of EZH2 inhibitors can include fatigue, nausea, and potential hematologic toxicities, but more data is needed to fully understand their safety profile in Hodgkin's Lymphoma.

What prior FDA approvals exist?

For the treatment of Hodgkin's Lymphoma, the FDA has approved several targeted therapies and immunotherapies. Brentuximab vedotin, an antibody-drug conjugate targeting CD30, is approved for classical Hodgkin's Lymphoma. Additionally, immune checkpoint inhibitors such as nivolumab and pembrolizumab, which target PD-1, have been approved for relapsed or refractory Hodgkin's Lymphoma. While Tazemetostat is an EZH2 inhibitor and not yet approved for Hodgkin's Lymphoma, these existing therapies represent the current landscape of targeted and immune-based treatments for the disease.

What other types of research exist?

Promising novel alternatives to Tazemetostat for Hodgkin's Lymphoma patients include: 1) Brentuximab vedotin, an antibody-drug conjugate targeting CD30, which has shown efficacy in relapsed or refractory cases. 2) Pembrolizumab and Nivolumab, both PD-1 inhibitors, have demonstrated significant activity in patients with relapsed or refractory Hodgkin's Lymphoma. 3) CAR T-cell therapies targeting CD30 are emerging as a potential option, with ongoing clinical trials showing encouraging results. These alternatives offer different mechanisms of action and have shown promise in recent clinical studies.

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EZH2 Inhibitor

Tazemetostat for Solid Cancers and Lymphoma

Phase 2

Waitlist Available

Led By Susan N Chi

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

For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3, Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment), Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions)

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as specified

Must not have

On complete blood count (CBC) differential, patients must not have any significant morphologic abnormalities concerning for myeloproliferative neoplasm (MPN)/myelodysplastic syndrome (MDS) or T- acute lymphoblastic leukemia (ALL)

Patients who have an uncontrolled infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well tazemetostat works in children with certain difficult-to-treat cancers that have specific gene mutations. Tazemetostat is a pill that aims to stop cancer cell growth by blocking a specific protein. The goal is to see if this treatment can help these children when other treatments have failed. Tazemetostat is already approved for treating various cancers, including certain brain tumors in children.

Who is the study for?

This trial is for patients with relapsed or refractory advanced solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with specific gene mutations (EZH2, SMARCB1, SMARCA4). Participants must have measurable disease and recovered from previous cancer therapies. They need adequate blood counts and organ function and can't have had prior EZH2 inhibitor treatment.

What is being tested?

The trial tests Tazemetostat's effectiveness in stopping tumor growth by blocking a protein called EZH2. It targets patients whose cancers haven't responded to other treatments and who carry certain genetic mutations that may be affected by this drug.

What are the potential side effects?

Potential side effects of Tazemetostat include fatigue, nausea, vomiting, constipation, decreased appetite and weight loss. There might also be changes in liver enzymes or blood cell counts leading to an increased risk of infections.

Eligibility Criteria

Inclusion Criteria

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

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My blood counts meet the required levels and I haven't needed platelet transfusions in the last week.

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My kidney function is normal or near normal.

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I am enrolled in APEC1621SC and assigned to MATCH in APEC1621C due to an actionable mutation.

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I have never taken tazemetostat or similar medications.

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Your bilirubin, SGPT (ALT), serum albumin, corrected QT (QTc) interval, and international normalized ratio (INR) need to be within certain levels.

Exclusion Criteria

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

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My blood tests do not show signs of specific blood disorders.

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I do not have any infections that are currently uncontrolled.

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I am not taking medication that strongly affects liver enzyme CYP3A4.

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I have a history of T-lymphoblastic lymphoma or leukemia.

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I do not have severe low blood counts or a history of bone marrow cancer.

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I have never had myeloid malignancies or myelodysplastic syndrome.

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I am taking medication to prevent graft-versus-host disease after a bone marrow transplant.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate (ORR)

Secondary study objectives

Percentage of Patients Experiencing Grade 3 or 4 Adverse Events

Progression-free Survival (PFS)

Other study objectives

Biomarker Predictors of Response to Tazemetostat

Change in Tumor Genomics

Side effects data

From 2021 Phase 2 trial • 20 Patients • NCT03456726

53%

Dysgeusia

41%

Nasopharyngitis

29%

Upper respiratory tract infection

29%

Blood creatine phosphokinase increased

29%

Lymphopenia

29%

Constipation

29%

Stomatitis

24%

Rash

18%

Weight decreased

18%

Blood creatinine increased

18%

Thrombocytopenia

18%

Neutropenia

18%

Nausea

12%

Influenza

12%

Amylase increased

12%

Herpes simplex

12%

Malaise

12%

Pneumonia

12%

Urinary tract infection

12%

Hypertriglyceridaemia

12%

Anaemia

12%

Hypophosphataemia

12%

Alopecia

12%

Eczema

Hypoalbuminaemia

Upper respiratory tract inflammation

Aspartate aminotransferase increased

Blood zinc decreased

Haematuria

Electrocardiogram QT prolonged

Skin exfoliation

Oedema peripheral

Gastroenteritis

Impetigo

Blood pressure decreased

Visual field defect

Hypogammaglobulinaemia

Osteonecrosis of jaw

Rash maculo-papular

Phlebitis

Nail disorder

Pyrexia

Myalgia

Gamma-glutamyltransferase increased

Insomnia

Traumatic intracranial haemorrhage

Hypertonic bladder

Fatigue

Musculoskeletal chest pain

Traumatic fracture

Gastric cancer

Non-small cell lung cancer

Haematochezia

Tooth disorder

Bronchitis

Abdominal pain

Large intestine polyp

Pneumocystis jirovecii pneumonia

Alanine aminotransferase increased

Immature granulocyte count increased

Cataract

Mechanical ileus

Atypical pneumonia

Periodontitis

Pneumonia aspiration

Leukopenia

Pericardial effusion

Conjunctival haemorrhage

Visual impairment

Epigastric discomfort

Oral herpes

Paronychia

Fall

Postoperative delirium

Procedural pain

Skin laceration

Tooth fracture

Hyperglycaemia

Hyperkalaemia

Hyperuricaemia

Pain in extremity

Tendon disorder

Myelodysplastic syndrome

Muscle spasticity

Peripheral motor neuropathy

Sciatica

Syncope

Asthma

Dysphonia

Erythema multiforme

Keloid scar

100%

80%

60%

40%

20%

Study treatment Arm

Participants With Follicular Lymphoma

Participants With Diffuse Large B-cell Lymphoma

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 (tazemetostat)Experimental Treatment1 Intervention

Patients receive tazemetostat PO BID on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tazemetostat

2016

Completed Phase 2

~1050

0 / 12Eligibility 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

Hodgkin's Lymphoma treatments often target specific molecular pathways to inhibit tumor growth and survival. For example, Tazemetostat, an EZH2 inhibitor, works by blocking the EZH2 enzyme, which is involved in the methylation of histones and regulation of gene expression. This inhibition can prevent the proliferation of cancer cells and induce apoptosis. Targeted therapies like this are crucial for Hodgkin's Lymphoma patients as they offer a more precise treatment approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

[New therapeutic strategies in non-Hodgkin lymphomas and Hodgkin lymphoma].