Tazemetostat + CHOP for T-Cell Lymphoma

Recruiting at 2 trial locations

Overseen By Eric Jacobsen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eric Jacobsen, MD

Must not be taking: Investigational agents

Disqualifiers: CNS involvement, Organ transplant, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of tazemetostat and CHOP chemotherapy for treating peripheral T-cell lymphoma (PTCL). Tazemetostat targets a specific protein linked to cancer growth, while CHOP is a common chemotherapy regimen for lymphoma. The trial includes two groups: one where participants will also undergo a stem cell transplant and one where they will not. It seeks individuals with PTCL who have not had more than one cycle of CHOP chemotherapy and have a tumor measurable on a CT scan. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on other investigational agents and should not have had prior chemotherapy for T-cell lymphoma, except for one cycle of CHOP/CHOEP or a short course of corticosteroids. It's best to discuss your current 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, when combined with CHOP therapy, may effectively treat certain types of lymphoma. In previous studies, most patients tolerated tazemetostat well, with common side effects including fatigue, nausea, and reduced appetite. Serious side effects were rare.

CHOP therapy, which includes cyclophosphamide, doxorubicin, vincristine, and prednisone, is a standard treatment for lymphoma. It often causes side effects like low blood cell counts, hair loss, and mouth sores, but doctors are skilled in managing these.

While detailed safety information on using tazemetostat with CHOP specifically for T-cell lymphoma is still being collected, both treatments have been used safely in other contexts. Prospective participants should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tazemetostat with CHOP therapy for T-cell lymphoma because Tazemetostat offers a novel mechanism of action compared to standard treatments. While traditional therapies like CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) work by attacking rapidly dividing cells, Tazemetostat specifically targets and inhibits EZH2, an enzyme that can drive cancer growth. This targeted approach could potentially enhance treatment effectiveness and minimize side effects. Additionally, for patients opting for a stem cell transplant, Tazemetostat's integration into the treatment regimen provides a potentially more effective way to maintain remission.

What evidence suggests that this trial's treatments could be effective for peripheral T-Cell Lymphoma?

Research has shown that tazemetostat, when combined with CHOP therapy, may help treat certain types of lymphomas. Tazemetostat blocks a protein called EZH2, which aids cancer cell growth, making it harder for these cells to survive. Previous studies found this combination effective and generally well-tolerated by patients. In this trial, participants will receive tazemetostat with CHOP therapy, with some also undergoing a stem cell transplant. While CHOP is already a common treatment for peripheral T-cell lymphoma (PTCL), adding tazemetostat might enhance its effectiveness. More research is ongoing, but early results are promising for those with PTCL. ^{1 2 3 6 7}

Who Is on the Research Team?

Eric Jacobsen, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with various types of T-cell lymphoma, including peripheral and intestinal forms. Participants should be suitable for chemotherapy. Specific eligibility criteria are not provided, but typically include factors like age, disease stage, and overall health.

Inclusion Criteria

My organs and bone marrow are working well.

Agree to use adequate contraception

Ability to understand and sign a written informed consent document

Exclusion Criteria

I have had an organ transplant.

I have nerve damage affecting my movements or sensations that is mild or worse.

I have not had major surgery in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Prephase

Participants receive a predetermined dose of Tazemetostat twice daily

2 weeks

1 visit (in-person)

Induction

Participants receive CHOP chemotherapy and Tazemetostat over 6 cycles of 21 days each

18 weeks

Multiple visits (in-person) for each cycle

Maintenance

Participants receive Tazemetostat daily for 6 cycles of 28 days each

24 weeks

Regular visits (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Melphalan
• Tazemetostat
• Vincristine

Trial Overview The study is testing the effectiveness of tazemetostat (an EZH2 inhibitor) combined with CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) against T-cell lymphoma. Some patients may also receive BEAM conditioning before a stem cell transplant.

How Is the Trial Designed?

Group I: Tazemetostat + CHOP Therapy + Transplant Not Elected Experimental Treatment 5 Interventions

Enrolled participants will complete: * Baseline visit * Prephase Period: Days -14 through -1: Predetermined dose of Tazemetost 2x daily * Induction Period: Cycles 1 through 6 (21 day cycles): * Cycle 1 Day 1: tumor biopsy and CT scan * Day 1: Predetermined dose of Cyclophosphamide once, Doxorubicin once, and Vincristine once * Days 1 through 5: Predetermined dose of Prednisone 1x daily * Days 2 through 21: Predetermined dose of Tazemetost 2x daily * Prior to Cycle 4 Day 1: Pet-CT scan * Note, treatment will stop if participants do not respond to the drugs after the first 3 cycles * Pet-CT scan at end of Cycle 6. * Maintenance Period: * Cycles 1 through 6 (28 day cycles): --Days 1 through 28: Predetermined dose of Tazemetost 2x daily. * After Cycle 3: CT scan * Cycle 4 Day 1: CT scan * End of treatment visit * Follow up is for 4 years

Group II: Tazemetostat + CHOP Therapy + Transplant Elected Experimental Treatment 9 Interventions

Enrolled participants will complete: * Baseline visit * Prephase Period: Days -14 through -1: Predetermined dose of Tazemetost 2x daily * Induction Period: Cycles 1 through 6 (21 day cycles): * Cycle 1 Day 1: tumor biopsy and CT scan * Day 1: Predetermined dose of Cyclophosphamide once, Doxorubicin once, and Vincristine once * Days 1 through 5: Predetermined dose of Prednisone 1x daily * Days 2 through 21: Predetermined dose of Tazemetost 2x daily * Prior to Cycle 4 Day 1: Pet-CT scan * Note, treatment will stop if participants do not respond to the drugs after the first 3 cycles * Bone marrow biopsy and Pet-CT scan at end of Cycle 6 * Maintenance Period: * Day 0: autologous stem cell transplant with BiCNU, Etoposide, Cytarabine, and Melphalan (BEAM) * Day 100: PET-CT scan * Cycles 1 through 6 (28 day cycles): --Days 1 through 28: Predetermined dose of Tazemetost 2x daily * After Cycle 3: CT scan * Cycle 4 Day 1: CT scan * End of treatment visit * Follow up is for 4 years

Doxorubicin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Adriamycin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in European Union as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Canada as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Approved in Japan as Doxorubicin for:

• Breast cancer
• Ovarian cancer
• Bladder cancer
• Lymphomas
• Leukemias
• Multiple myeloma
• Kaposi's sarcoma
• Soft tissue sarcomas

Who Is Running the Clinical Trial?

Eric Jacobsen, MD

Lead Sponsor

Trials

1

Recruited

20+

Ipsen

Industry Sponsor

Trials

358

Recruited

74,600+

David Loew

Ipsen

Chief Executive Officer since 2020

BA in Business Administration and MBA from the University of St. Gallen, Switzerland

Sandra Silvestri

Ipsen

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

In a study of 101 lymphoma patients undergoing autologous stem cell transplantation, the mitoxantrone-melphalan (Mx-Mel) regimen showed similar efficacy to the BEAM regimen while being less toxic, making it a promising alternative for patients who cannot tolerate high cytotoxic treatments.

Although the BEAM regimen resulted in a statistically shorter time to neutrophil engraftment (10 days) compared to Mx-Mel (12 days), both regimens did not lead to significant differences in transplant-related complications, indicating that Mx-Mel is a safe option with effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens in Patients with Lymphoma. Gunes, AK., Serin, I., Demir, I., et al.[2023]

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]

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]

In a study testing 11 anti-cancer agents on 4 pediatric ALCL cell lines, vinblastine was found to be the most effective, significantly inhibiting cell growth in a time- and dose-dependent manner, with effective doses as low as 0.0002 microM/L after 24 hours.

Vinblastine treatment not only inhibited cell growth but also induced apoptosis and disrupted mitotic spindle formation, supporting its use as a first-line treatment in high-risk pediatric ALCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro. Muto, A., Nakagawa, A., Shimomura, Y., et al.[2019]

Targeted therapies combined with doxorubicin showed significant effectiveness against small cell sarcoma cell lines, with dual combinations of vorinostat and 17-DMAG achieving synergistic effects that enhanced cell killing by 60% compared to doxorubicin alone.

The study found that while vorinostat and 17-DMAG synergized with doxorubicin, sorafenib did not, and the combination of all three agents did not show synergy but increased apoptosis, indicating potential for improved treatment strategies in advanced sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted polytherapy in small cell sarcoma and its association with doxorubicin. Dumont, SN., Yang, D., Dumont, AG., et al.[2021]

In a study of 93 children with acute lymphoblastic leukemia, both the Capizzi regimen (escalating doses of methotrexate) and high-dose methotrexate (HD-MTX) showed similar overall toxicity rates, with 28.7% for Capizzi and 29.8% for HD-MTX, indicating that both regimens are associated with significant toxicities.

Mucositis was more prevalent in the HD-MTX group (14.6%) compared to the Capizzi group (5.5%), suggesting that while both regimens are effective, HD-MTX may carry a higher risk for this specific toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects with intravenous methotrexate in children with acute lymphoblastic leukemia/lymphoma: a retrospective study. Mandal, P., Samaddar, S., Chandra, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06692452

Tazemetostat Plus CHOP in 1L T-cell Lymphoma This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as a ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/555935

Tazemetostat Plus CHOP in 1L T-cell Lymphoma This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) ...

3. dana-farber.org dana-farber.org/clinical-trials/24-462

A phase II study of tazemetostat in combination with CHOP ... This research is being done to evaluate tazemetostat in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy as a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12036195/

A multicenter, open-label, single-arm, phase Ib clinical trial of ... HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase ...

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

Efficacy of tazemetostat in combination with R-CHOP ... In the phase I Epi-RCHOP study (NCT02889523), we reported that R-CHOP-tazemetostat was well tolerated with the recommended phase II dose, consistent with ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-10764

Tazemetostat in Combination with CHOP for Previously ... This phase II trial tests how well tazemetostat in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) works in treating ...

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

213400Orig1s000 - accessdata.fda.gov ... Tazemetostat and CHOP Combination Treatment (WSU‐DLCL2). *CHOP = Cyclophosphamide, doxorubicin, vincristine, prednisone. Cyclophosphamide ...