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

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: Tazemetostat Pill

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05934838

22-07025095

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Tazemetostat and CAR T-Cell Therapy

Experimental group

Description:

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

Treatment:

Drug: Tazemetostat Pill