Clinical trial NCT05934838: A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas
Official title: A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Follicular Lymphoma
B-Cell Lymphoma
Mantle Cell Lymphoma
Diffuse Large B Cell Lymphoma
Keywords: CAR T-cell
Tazemetostat
FL
MCL
DLBCL
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Epizyme, Inc.
name: Applebaum Foundation
name: American Society of Clinical Oncology
First posted: 2023-07-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants who experience adverse events classified per CTCAEv5
timeFrame: From start of treatment until 30 days after the last dose of tazemetostat, for a maximum of approximately 13 months
Secondary outcomes:
measure: Number of patients who experience cytokine release syndrome (CRS) by ASTCT Consensus Grading system during therapy
timeFrame: From start of treatment until Day 21 days following CAR T cell infusion
measure: Number of patients who experience immune effector cell neurotoxicity syndrome (ICANS) by ASTCT Consensus Grading system during therapy
timeFrame: From start of treatment until Day 21 days following CAR T cell infusion
measure: Overall response rate (ORR) reported as per Lugano response criteria
timeFrame: From start of treatment until disease progression or death, for a maximum of approximately 6 years
measure: Mean Progression-Free Survival (PFS)
timeFrame: From start of treatment until disease progression or death, for a maximum of approximately 6 years
measure: Mean Overall Survival (OS)
timeFrame: From start of treatment until death, for a maximum of approximately 6 years
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine/NewYork-Presbyterian Hospital
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Samuel Yamshon, M.D.
role: PRINCIPAL_INVESTIGATOR
References: