Tazemetostat + Belinostat for Lymphoma

Recruiting at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, UGT1A1 inhibitors

Disqualifiers: CNS metastases, Allergic reactions, others

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

Compensation: Varies

Number of Visits: 23

Duration: Up to 2 years

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the safest dose and test the side effects of a combination treatment using tazemetostat and belinostat for patients with lymphoma that has returned or doesn't respond to treatment. Tazemetostat stops cancer cell growth by blocking a specific enzyme, while belinostat (also known as Beleodaq) may kill cancer cells and enhance their responsiveness to other drugs. Individuals with non-Hodgkin lymphoma who haven't succeeded with at least two systemic therapies and are not eligible for stem cell or CAR T-cell therapy might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot take strong or moderate inhibitors or inducers of CYP3A4 within 14 days before the trial. It's important to discuss your current medications with the trial team to avoid any interactions.

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

Research has shown that both tazemetostat and belinostat have been studied for safety in patients with certain types of lymphoma. Tazemetostat, for instance, has proven effective in treating relapsed or hard-to-treat follicular lymphoma, particularly in patients with an EZH2 mutation, indicating it is generally well-tolerated in similar patient groups.

Belinostat is already approved for use in some cancers, so its safety profile is well understood. However, when these two drugs are combined, researchers are still testing to determine the best dose and understand their interaction in the body.

As this is a phase 1 trial, the primary focus is on assessing the safety and side effects of the drug combination. While the safety of each drug individually is known, the safety of their combined use remains under study. Researchers will closely monitor participants to manage any side effects and ensure the treatment remains as safe as possible. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tazemetostat and belinostat for treating lymphoma because it brings a unique approach compared to standard treatments like chemotherapy and radiation. Tazemetostat works by inhibiting EZH2, an enzyme that can help cancer cells grow, while belinostat is a histone deacetylase inhibitor that disrupts cancer cell function, making them more susceptible to treatment. This combination aims to target cancer cells more precisely, potentially leading to better outcomes with fewer side effects. Unlike traditional treatments, which can be harsh and non-specific, this pair targets specific pathways in cancer cells, offering a promising new strategy for tackling lymphoma.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that tazemetostat, a type of medication, effectively treats follicular lymphoma that has returned or resisted other treatments, particularly in patients with an EZH2 mutation. Belinostat blocks certain enzymes that cancer cells need to grow, helping to kill these cells. Early studies in animals and labs suggest that combining tazemetostat and belinostat might shrink or control cancer. This trial will evaluate the effectiveness of this combination in people with lymphoma, as its efficacy in this patient population remains unknown. ^{1 4 6 7 8}

Who Is on the Research Team?

Jennifer E Amengual

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with certain types of lymphoma that have come back or haven't responded to treatment can join this trial. They should have tried 1-5 previous treatments, be in fairly good health, and not planning on stem cell or CAR T-cell therapy. People with serious illnesses, pregnant women, and those who've had recent other cancer therapies are excluded.

Inclusion Criteria

Patients must have measurable disease according to the Lugano classification

My heart condition allows me to perform daily activities with slight limitations.

My hepatitis B virus load is undetectable with treatment.

Exclusion Criteria

I have recovered from side effects of previous cancer treatments, except for hair loss.

Patients who are receiving any other investigational agents

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tazemetostat orally twice daily and belinostat intravenously on days 1-5 of each 21-day cycle

Up to 2 years

Visits every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Long-term follow-up

Participants are followed up every 3 months for a year or until they begin a new treatment for their disease

1 year

Quarterly visits

What Are the Treatments Tested in This Trial?

Interventions

• Belinostat
• Tazemetostat

Trial Overview

The trial is testing the safety and best dose of tazemetostat combined with belinostat for relapsed/refractory lymphomas. These drugs block enzymes that help cancer cells grow. The study will see if this combo can shrink or stabilize cancer as it has done in animal studies.

How Is the Trial Designed?

Group I: Treatment (tazemetostat, belinostat) Experimental Treatment 7 Interventions

Patients receive tazemetostat PO BID on days 2-21 of cycle 1 and days 1-21 of subsequent cycles, and belinostat IV over 30-180 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo a tumor biopsy during screening and on study (dose-expansion only). Patients undergo blood sample collection while on study and CT or PET/CT scan throughout the study.

Belinostat is already approved in United States for the following indications:

Approved in United States as Beleodaq for:

• Peripheral T-cell lymphoma (PTCL)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Belinostat is a small-molecule inhibitor that targets multiple classes of histone deacetylase enzymes and has been specifically developed for treating relapsed or refractory peripheral T-cell lymphoma (PTCL).

It has received accelerated approval from the FDA as a monotherapy for PTCL, marking a significant milestone in its development and offering a new treatment option for patients with this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat: first global approval. Poole, RM.[2021]

The combination of pralatrexate (PLX) and belinostat (BLS) showed an additive effect in various lymphoma cell lines, indicating that they can work together effectively to inhibit cancer cell growth.

BLS significantly increased the sensitivity of lymphoma cells to PLX, suggesting that using BLS could enhance the efficacy of PLX treatment, particularly in B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedule-Dependent Synergy Between the Histone Deacetylase Inhibitor Belinostat and the Dihydrofolate Reductase Inhibitor Pralatrexate in T-and B-cell Lymphoma Cells in vitro. Peters, GJ., van Gemert, FPA., Kathmann, I., et al.[2020]

Belinostat, a histone deacetylase inhibitor, received accelerated FDA approval for treating relapsed or refractory peripheral T-cell lymphoma (PTCL) based on a trial involving 120 patients, showing an overall response rate of 25.8%.

The treatment demonstrated a median duration of response of 8.4 months, with common side effects including nausea and fatigue, and notable grade 3/4 toxicities such as anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma. Lee, HZ., Kwitkowski, VE., Del Valle, PL., et al.[2015]

The FDA has granted accelerated approval for Beleodaq, a histone deacetylase inhibitor, specifically for patients with relapsed or refractory peripheral T-cell lymphoma.

This approval indicates that Beleodaq has shown promising efficacy in treating this type of lymphoma, which is important for patients who have not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beleodaq approved for rare lymphomas. [2014]

Belinostat, when combined with doxorubicin, was well tolerated in a study of 41 patients, with a maximum tolerated dose established at 1000 mg/m² for belinostat and 75 mg/m² for doxorubicin, despite common side effects like fatigue and nausea.

The combination therapy showed a moderate response rate of 13% in soft tissue sarcomas, with a median time to progression of 6.0 months, suggesting it may be more effective than doxorubicin alone in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas. Vitfell-Rasmussen, J., Judson, I., Safwat, A., et al.[2020]

Belinostat is an effective treatment for relapsed or refractory peripheral T-cell lymphoma (PTCL), showing an overall response rate of 25.8% and a median duration of response of 8.4 months in clinical trials.

The treatment is generally well tolerated, with common side effects including nausea, vomiting, fatigue, pyrexia, and anemia, affecting more than 25% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. Campbell, P., Thomas, CM.[2017]

In a study involving 23 patients with previously untreated peripheral T-cell lymphoma, the combination of belinostat and CHOP was well tolerated, with the maximum tolerated dose (MTD) established at 1000 mg/m2 over a Day 1-5 schedule.

The treatment showed a high overall response rate (ORR) of 86%, with 71% of patients achieving a complete response (CR) at the MTD, indicating its efficacy in treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma. Johnston, PB., Cashen, AF., Nikolinakos, PG., et al.[2021]

Citations

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This phase I trial tests the safety, side effects, and best dose of combination therapy with tazemetostat and belinostat in treating patients with lymphoma ...

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ASH 2024 | Update on ETCTN P10500, a Phase I study of ...

A Phase I clinical trial (NCT05627245) of tazemetostat plus belinostat for the treatment of relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

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This phase I trial tests the safety, side effects, and best dose of combination therapy with tazemetostat and belinostat in treating ...

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