Tazemetostat for Lymphoma

Overseen By Margaret Thomas, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, Recent stem cell transplant, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a drug called tazemetostat for treating peripheral T-cell lymphoma, a type of blood cancer. Tazemetostat has already received approval for other lymphomas, but this study examines its effectiveness for this specific type. People whose lymphoma has returned or not responded to other treatments might be suitable candidates. Participants must have a diagnosis of specific T-cell lymphomas and must have tried at least one other treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain immunosuppressive medications or high doses of corticosteroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tazemetostat is generally safe for treating certain types of lymphoma. In a previous study, patients with relapsed or hard-to-treat follicular lymphoma experienced a relatively low rate of severe side effects. Serious side effects occurred in about 30% of patients, with some side effects affecting 2% or more of those taking the medication.

Tazemetostat poses fewer safety risks compared to similar treatments like idelalisib and duvelisib, while maintaining effectiveness. The FDA has already approved this treatment for certain conditions, indicating a level of safety confidence in the medical community. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Tazemetostat is unique because it specifically targets and inhibits the EZH2 enzyme, which plays a role in the growth and survival of certain cancer cells, like those in T-cell lymphomas. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, Tazemetostat offers a more targeted approach, potentially leading to fewer side effects. Researchers are excited about this treatment because it opens up new possibilities for patients who have not responded well to existing therapies, offering hope for more effective and personalized treatment options.

What evidence suggests that tazemetostat might be an effective treatment for peripheral T-cell lymphoma?

Research has shown that tazemetostat, which participants in this trial may receive, may effectively treat certain types of lymphoma. In patients with relapsed or refractory (R/R) follicular lymphoma, tazemetostat led to tumor shrinkage in 55% of cases. Specifically, more than half of the patients experienced tumor reduction. Additionally, almost half of these patients did not experience disease progression for a year. While this study focused on follicular lymphoma, researchers hope that tazemetostat could also benefit other lymphomas, such as peripheral T-cell lymphoma, because it targets EZH2, a protein that can promote cancer growth. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults with certain types of peripheral T-cell lymphoma (PTCL) that have come back or haven't responded to treatment can join. They need good liver and kidney function, stable heart performance, and no dependence on blood transfusions. People with HIV, Hepatitis B or C are eligible if their conditions are well-managed. Women who can have children must not be pregnant, agree to pregnancy tests, and use effective birth control.

Inclusion Criteria

I have Hepatitis B but am on treatment and my viral load is undetectable.

Willing and able to participate in all required evaluations and procedures in the study protocol

Non-childbearing potential defined

Exclusion Criteria

I had a stem cell transplant using my own cells within the last 3 months.

My cancer has spread to my brain or spinal cord.

Pregnant women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tazemetostat to evaluate safety and tolerability in relapsed/refractory peripheral T-cell lymphoma

4 weeks

Cycle 1: 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Tazemetostat

Trial Overview The trial is testing Tazemetostat, an oral medication designed to inhibit a protein called EZH2 in patients with specific lymphoid malignancies. It's for those whose disease has returned after treatment or hasn't improved at all despite previous therapies.

How Is the Trial Designed?

Group I: Cohort A Experimental Treatment 1 Intervention

T-cell Lymphomas

Tazemetostat is already approved in United States, European Union for the following indications:

Approved in United States as Tazverik for:

• Epithelioid sarcoma
• Follicular lymphoma

Approved in European Union as Tazverik for:

• Epithelioid sarcoma

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Carfilzomib (CFZ) is an effective second-generation proteasome inhibitor approved for treating relapsed and refractory multiple myeloma, showing promising results even in patients with renal insufficiency and no significant impact from cytogenetic abnormalities.

Pomalidomide (POM) is a novel immunomodulatory drug with strong anti-myeloma effects, approved for patients who have not responded to previous therapies, and it has demonstrated high efficacy in those with high-risk cytogenetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. Jurczyszyn, A., Legieć, W., Helbig, G., et al.[2021]

Recent FDA approvals of novel agents vorinostat, romidepsin, and pralatrexate have significantly transformed the treatment landscape for cutaneous T cell lymphoma (CTCL).

These new therapies provide additional options for patients, enhancing the effectiveness of CTCL management alongside existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic advances in cutaneous T-cell lymphoma. Akilov, OE., Geskin, L.[2022]

In a phase 1 study involving 20 B-cell lymphoma patients, the combination of carfilzomib and vorinostat was found to have a maximum tolerated dose of 20 mg/m2 for carfilzomib and 100 mg for vorinostat, with dose-limiting toxicities including grade 3 pneumonitis and febrile neutropenia.

While one patient experienced a partial response and two had stable disease, changes in biomarkers like NF-κB activation and Bim levels did not correlate with clinical outcomes, suggesting that further research is needed to understand the efficacy of this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of carfilzomib (PR-171) in combination with vorinostat (SAHA) in patients with relapsed or refractory B-cell lymphomas. Holkova, B., Kmieciak, M., Bose, P., et al.[2019]

The selective HDAC6 inhibitor citarinostat (ACY-241) shows a favorable safety profile and enhances the effectiveness of pomalidomide in treating multiple myeloma, promoting greater cancer cell death and cell cycle arrest in laboratory tests.

In a mouse model of multiple myeloma, the combination of ACY-241 and pomalidomide significantly inhibited tumor growth, suggesting that this combination therapy could be a promising approach for patients with multiple myeloma and other B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of pomalidomide anti-tumor response with ACY-241, a selective HDAC6 inhibitor. North, BJ., Almeciga-Pinto, I., Tamang, D., et al.[2019]

In a study involving 37 patients with untreated peripheral T-cell lymphoma, romidepsin was found to be safely combined with CHOP therapy, with a recommended dose of 12 mg/m² established for further testing.

While the combination showed promise, it also resulted in significant side effects, including high rates of neutropenia and thrombocytopenia, indicating the need for careful monitoring and further randomized trials to assess its efficacy compared to CHOP alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study. Dupuis, J., Morschhauser, F., Ghesquières, H., et al.[2018]

Citations

1. tazverik.com tazverik.com/hcp/follicular-lymphoma/clinical-trial-results

Clinical Trial Results in R/R Follicular Lymphoma Efficacy results, including overall response rate (ORR) and duration of response (DOR) with TAZVERIK® (tazemetostat) in R/R follicular lymphoma patients ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19045

Efficacy and safety of oral tazemetostat, an EZH2 inhibitor, ... The results showed a 55% tumor response rate and 49.6% progression-free survival (PFS) at 1 year, but only 10% achieved PFS at 2 years.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8427481/

Tazemetostat for patients with relapsed or refractory follicular ... In a phase 1 trial, monotherapy with tazemetostat showed anticancer activity and a favourable safety profile in patients with relapsed or refractory non- ...

4. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00089-6/fulltext

Efficacy of tazemetostat in combination with R-CHOP ... After a median follow-up of 18.5 months (IQR: 15.4–21), estimated progression-free and overall survival at 18 months were 77.7% (95% CI: 67.5–85.1%) and 88.8% ( ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2020/213400Orig1s000MultidisciplineR.pdf

213400Orig1s000 - accessdata.fda.gov Integrated Assessment of Effectiveness. The efficacy of tazemetostat for the treatment of patients with R/R follicular lymphoma whose tumors ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8989805/

Tazemetostat was Associated with a Lower Risk for Safety ... Tazemetostat was associated with lower RR for safety outcomes versus idelalisib, duvelisib, copanlisib, and umbralisib, while achieving similar efficacy ...

7. tazverik.com tazverik.com/hcp/follicular-lymphoma/safety-and-tolerability

Safety & Tolerability in R/R Follicular Lymphoma Serious adverse reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions occurring in ≥2% of patients taking TAZVERIK included ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19064

Efficacy and safety of tazemetostat in patients with ... Relapsed/refractory FL and DLBCL responds well to Tazemetostat in terms of ORR, PFS, and DOR, with a relatively low incidence of severe adverse events.