Tazemetostat + Belinostat for Lymphoma

Recruiting at 9 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

Trial Summary

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.

What data supports the idea that Tazemetostat + Belinostat for Lymphoma is an effective treatment?

The available research shows that Belinostat, one of the drugs in the combination, has been approved for treating a type of lymphoma called peripheral T-cell lymphoma (PTCL). It was shown to help about 25.8% of patients, with some experiencing a complete or partial reduction in their cancer. Although there is no specific data on the combination of Tazemetostat and Belinostat for lymphoma, Belinostat has shown promise in making other drugs more effective in lab studies. This suggests that the combination could potentially be effective, but more research is needed to confirm this. ^{1 2 3 4 5}

What safety data is available for the treatment of Tazemetostat and Belinostat in lymphoma?

Belinostat, also known as Beleodaq, is a histone deacetylase inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). Safety data from clinical trials indicate that common adverse reactions include nausea, fatigue, pyrexia, anemia, and vomiting. Grade 3/4 toxicities include anemia, thrombocytopenia, dyspnea, neutropenia, fatigue, and pneumonia. In combination with other treatments, Belinostat has been generally well tolerated, with fatigue, nausea, and alopecia being common adverse events. The combination of Belinostat with other drugs has shown moderate response rates and is considered safe and effective for PTCL. ^{1 3 4 6 7}

Is the drug Belinostat a promising treatment for lymphoma?

Yes, Belinostat is a promising drug for treating lymphoma. It has been approved by the FDA for treating a type of lymphoma called peripheral T-cell lymphoma. It works by targeting specific enzymes in cancer cells, which can help stop their growth. This approval shows that it has potential in helping patients with this condition. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase I trial tests the safety, side effects, and best dose of combination therapy with tazemetostat and belinostat in treating patients with lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Tazemetostat is in a class of medications called EZH2 inhibitors. The EZH2 gene provides instructions for making a type of enzyme called histone methyltransferase which is involved in gene expression and cell division. Blocking EZH2 may help keep cancer cells from growing. Belinostat is in a class of medications called histone deacetylase inhibitors. Histone deacetylases are enzymes needed for cell division. Belinostat may kill cancer cells by blocking histone deacetylase. It may also prevent the growth of new blood vessels that tumors need to grow and may help make cancer cells easier to kill with other anticancer drugs. There is some evidence in animals and in living human cells that combination therapy with tazemetostat and belinostat can shrink or stabilize cancer, but it is not known whether this will happen in people. This trial may help doctors learn more about treatment of patients with relapsed or refractory lymphoma.

Research Team

Jennifer E Amengual

Principal Investigator

Yale University Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Belinostat: first global approval. [2021]

2. Switzerland 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. [2020]

3. England 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

FDA Approval: Belinostat for the Treatment of Patients with Relapsed or Refractory Peripheral T-cell Lymphoma. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Beleodaq approved for rare lymphomas. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. [2017]

7. Egypt pubmed.ncbi.nlm.nih.gov

A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas. [2020]