Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Tazemetostat is being administered prior to, and following, standard of care CAR T cell therapy. The use of tazemetostat in this way is investigational.

Participants will take 800 mg of tazemetostat twice a day starting 7 days before apheresis and continue to take tazemetostat until lymphodepletion, which is chemotherapy given prior to receiving the CAR T cells. Participants will stop taking tazemetostat after lymphodepletion until after CAR T cell infusion. Once lymphocyte counts increase, tazemetostat will be resumed and tazemetostat will be taken for 6 - 12 months, depending on participant response.

Tazemetostat Pill

Danielle Guarneri

Samuel Yamshon, MD

Samuel Yamshon, M.D.

This is a clinical trial to evaluate the feasibility and safety of giving tazemetostat followed by standard of care CAR T cell infusion in previously treated diffuse large b-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety. Participants will receive the tazemetostat pills before and after receiving their CAR T cell therapy, for up to 12 months after CAR T cell administration. Patients will be followed for up to 5 years.

This is a single arm, open label, clinical trial to evaluate the feasibility and safety of oral tazemetostat followed by standard of care CAR T cell infusion in previously treated DLBCL, FL, and MCL. The investigators hypothesis is that this combination has the potential to significantly improve the ability of CART cells to recognize and kill lymphoma cells without a significant impact on safety.

Tazemetostat 800 mg will be given twice daily by mouth for at least 1 week prior to apheresis, during the period between apheresis and CAR T infusion, and following lymphodepletion chemotherapy until Day 7 post-CAR T therapy. Once patients' platelets and neutrophil counts recover, tazemetostat will be resumed. Tazemetostat treatment will continue for up to 6 months in patients with complete responses and up to 12 months in patients with partial responses.

A 3+3 trial design will be implemented for the first six patients enrolled. The regimen will be considered feasible if at least 12 out of 15 subjects are able to receive at least 2 weeks of tazemetostat, generate the CAR T cell product and receive CAR T cell therapy.

A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas

Adverse reactions will be graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Patients will undergo screening for CRS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines

Patients will undergo screening for ICANS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines

Overall response rate will be reported as the number of participants who achieve a complete or partial response per the Lugano response criteria

PFS is defined as the duration of time from start of treatment to time of documentation of progression or death from any cause.

OS is defined as the duration of time from start of treatment to death from any cause.

Epizyme, Inc.

Applebaum Foundation

American Society of Clinical Oncology

Weill Medical College of Cornell University

50 patients will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation.

Mosunetuzumab will be administered in weekly dose increments ("step-up dosing") during Cycle 1 and then on Day 1 of each cycle. Mosunetuzumab will be given in 28-day cycles for up to 12 cycles. Mosunetuzumab will be administered SC at the dose of 5 mg on Day 1, 45 mg on Day 8, and 45 mg on Day 15 in Cycle 1. Beginning with Cycle 2, it will be administered SC at the dose of 45 mg on Day 1. Each cycle lasts 4 weeks.

Mosunetuzumab

Oral tazemetostat will be administered by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation until disease progression, unacceptable toxicity, or consent is withdrawn. Patients will remain on tazemetostat for up to twelve 28-day cycles from initiation of mosunetuzumab.

Tejasvi Kaur Sahni

Brittany Hobbie

The goal of this study is to learn about the safety and effectiveness of the combination of tazemetostat pills in combination with mosunetuzumab injections for people with follicular lymphoma who haven't received treatment before. The investigators hypothesize that tazemetostat with mosunetuzumab has the potential to increase the efficacy of the product without compromising the safety.

Tazemetostat is a drug that inhibits EZH2, an enzyme known to drive the development of B-cell lymphomas, and inhibiting it appears to have many effects that slow down lymphoma growth and enhance the immune system's ability to fight it. Tazemetostat is FDA-approved in previously treated follicular lymphoma and currently undergoing study in other lymphomas.

Mosunetuzumab is a bispecific antibody therapy that is a therapeutic strategy that uses the immune system to fight lymphoma, called immunotherapy. Bispecific antibodies have two ends: one attaches to T cells in the immune system and the other attaches to lymphoma cells, helping guide our immune system to attack the cancer. Mosunetuzumab has been studied in follicular lymphoma that has previously been treated, with positive results. Mosunetuzumab is approved by the FDA to be given intravenously (directly into a vein) but is not yet approved by the FDA is not yet approved as an injection under the skin, which is how it is given in this study. They have not yet been studied in combination.

This is a phase II, open-label study. Fifty patients with previously untreated follicular lymphoma will be enrolled and treated with standard dosing of subcutaneous mosunetuzumab, and with oral tazemetostat by mouth twice daily at standard dosing (800 mg twice daily) beginning at the same time as mosunetuzumab initiation. Mosunetuzumab and tazemetostat will be given in 28-day cycles for up to 12 cycles. Response assessments by PET/CT will occur at 12 weeks post-mosunetuzumab and again at 30 and 48 weeks for those with an ongoing response to treatment. Treatment with steroids, tocilizumab, growth factors, tumor lysis prophylaxis, and antibiotics may be used as per standard of care at our institution. Dose modifications are permitted for toxicity. There will be a follow-up visit after 2 years from starting the study.

Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma

A Phase II Trial of Tazemetostat Plus Mosunetuzumab in Untreated Follicular Lymphoma

The proportion of patients who achieve complete response as per the Lugano criteria will be calculated and their 90% confidences will be computed with Clopper-Pearson method via exact binomial distribution.

CRS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

ICANS will be assessed per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

PFS is defined as the duration of time from start of treatment to time of progression or death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.

OS is defined as the duration of time from start of treatment to death from any cause. Patients will be followed for a maximum of approximately 10 years from the start of treatment.

ORR is defined as the proportion of patients who have a partial or complete response to therapy

Response and progression are evaluated according to the Lugano criteria for lymphoma response.

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease or death due to any cause, whichever occurs first is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas	NCT05934838	Follicular Lymp... B-Cell Lymphoma Mantle Cell Lym... Diffuse Large B...	Tazemetostat Pi...	18 Years -	Weill Medical College of Cornell University
A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas	NCT05934838	Follicular Lymp... B-Cell Lymphoma Mantle Cell Lym... Diffuse Large B...	Tazemetostat Pi...	18 Years -	Weill Medical College of Cornell University
A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas	NCT05934838	Follicular Lymp... B-Cell Lymphoma Mantle Cell Lym... Diffuse Large B...	Tazemetostat Pi...	18 Years -	Weill Medical College of Cornell University
Tazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma	NCT05994235	Follicular Lymp...	Mosunetuzumab Tazemetostat Pi...	18 Years -	Weill Medical College of Cornell University

Spots Global Cancer Trial Database for tazemetostat pill