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

Mantle Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05934838
• Other study ID #: 22-07025095
• Status: Recruiting
• Phase: Phase 1
• Start date: October 4, 2023
• Est. completion date: September 2031

Study information

• Verified date: October 2023
• Source: Weill Medical College of Cornell University
• Contact: Danielle Guarneri
• Phone: 212-746-0974
• Email: dag2037[@]med.cornell.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: September 2031
• Est. primary completion date: September 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
United States	Weill Cornell Medicine/NewYork-Presbyterian Hospital	New York	New York

Sponsors (4)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	American Society of Clinical Oncology, Applebaum Foundation, Epizyme, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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