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

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.

Study Overview

• Status: Recruiting
• Conditions: Follicular Lymphoma; Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma; B-Cell Lymphoma
• Intervention / Treatment: Drug: Tazemetostat Pill

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Danielle Guarneri; Phone Number: 212-746-0974; Email: dag2037@med.cornell.edu
• Study Contact Backup: Name: Samuel Yamshon, MD; Phone Number: 646-962-7950; Email: sjy9001@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine/NewYork-Presbyterian Hospital
      • Contact: Danielle Guarneri; Phone Number: 212-746-0974; Email: dag2037@med.cornell.edu
      • Contact: Samuel Yamshon, MD; Email: sjy9001@med.cornell.edu
      • Principal Investigator: Samuel Yamshon, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of DLBCL, FL, or MCL
• Eligible to receive standard of care CAR T cells
• Have received at least 2 prior therapies

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Tazemetostat and CAR T-Cell Therapy; 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; 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.; Other Names: Tazverik

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients who experience cytokine release syndrome (CRS) by ASTCT Consensus Grading system during therapy	Patients will undergo screening for CRS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines	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	Patients will undergo screening for ICANS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines	From start of treatment until Day 21 days following CAR T cell infusion
Overall response rate (ORR) reported as per Lugano response criteria	Overall response rate will be reported as the number of participants who achieve a complete or partial response per the Lugano response criteria	From start of treatment until disease progression or death, for a maximum of approximately 6 years
Mean Progression-Free Survival (PFS)	PFS is defined as the duration of time from start of treatment to time of documentation of progression or death from any cause.	From start of treatment until disease progression or death, for a maximum of approximately 6 years
Mean Overall Survival (OS)	OS is defined as the duration of time from start of treatment to death from any cause.	From start of treatment until death, for a maximum of approximately 6 years

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Epizyme, Inc.; American Society of Clinical Oncology; Applebaum Foundation
• Investigators: Principal Investigator: Samuel Yamshon, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2031

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL; FL; MCL; CAR T-cell; Tazemetostat
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell
• Other Study ID Numbers: 22-07025095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No