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

NCT05934838 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-07025095
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Follicular Lymphoma; B-Cell Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma

Keywords

CAR T-cell; Tazemetostat; FL; MCL; DLBCL

Outcome Measures

Primary Outcomes (1)

• Number of participants who experience adverse events classified per CTCAEv5

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

  From start of treatment until 30 days after the last dose of tazemetostat, for a maximum of approximately 13 months

Secondary Outcomes (5)

• Number of patients who experience cytokine release syndrome (CRS) by ASTCT Consensus Grading system during therapy

  From start of treatment until Day 21 days following CAR T cell infusion

• Number of patients who experience immune effector cell neurotoxicity syndrome (ICANS) by ASTCT Consensus Grading system during therapy

  From start of treatment until Day 21 days following CAR T cell infusion

• Overall response rate (ORR) reported as per Lugano response criteria

  From start of treatment until disease progression or death, for a maximum of approximately 6 years

• Mean Progression-Free Survival (PFS)

  From start of treatment until disease progression or death, for a maximum of approximately 6 years

• Mean Overall Survival (OS)

  From start of treatment until death, for a maximum of approximately 6 years

Study Arms (1)

Tazemetostat and CAR T-Cell Therapy

EXPERIMENTAL

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

Drug: Tazemetostat Pill

Interventions

Tazemetostat Pill DRUG

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.

Also known as: Tazverik

Tazemetostat and CAR T-Cell Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of DLBCL, FL, or MCL
• Eligible to receive standard of care CAR T cells
• Have received at least 1 prior therapies

You may not qualify if:

• Active viral infection with HIV or hepatitis type B or C
• Active, uncontrolled systemic fungal, bacterial or viral infection
• Active treatment for another cancer
• Pregnant or breastfeeding
• Unable to take oral medication
• Certain significant past medical history, such recent stroke, pulmonary embolism, myocardial infarction, congestive heart failure, uncontrolled hypertension, or certain arrhythmias

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Epizyme, Inc.: collaborator
• Applebaum Foundation: collaborator
• American Society of Clinical Oncology: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Samuel Yamshon, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicole Santos

CONTACT

646-962-6827; nis7058@med.cornell.edu

Samuel Yamshon, MD

CONTACT

646-962-7950; sjy9001@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 7, 2023
• Study Start: October 4, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)