A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Number of participants who experience adverse events classified per CTCAEv5 [From start of treatment until 30 days after the last dose of tazemetostat, for a maximum of approximately 13 months]
Adverse reactions will be graded as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Secondary Outcome Measures
- 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]
Patients will undergo screening for CRS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines
- 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]
Patients will undergo screening for ICANS per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines
- 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]
Overall response rate will be reported as the number of participants who achieve a complete or partial response per the Lugano response criteria
- Mean Progression-Free Survival (PFS) [From start of treatment until disease progression or death, for a maximum of approximately 6 years]
PFS is defined as the duration of time from start of treatment to time of documentation of progression or death from any cause.
- Mean Overall Survival (OS) [From start of treatment until death, for a maximum of approximately 6 years]
OS is defined as the duration of time from start of treatment to death from any cause.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Weill Cornell Medicine/NewYork-Presbyterian Hospital | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Epizyme, Inc.
- Applebaum Foundation
- American Society of Clinical Oncology
Investigators
- Principal Investigator: Samuel Yamshon, M.D., Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 22-07025095