Study of Tazemetostat in Lymphoid Malignancies

NCT05983965 | Terminated Phase 1 FDA Drug

• 2 other identifiers: IRB-300011353Robert Award
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Tazemetostat is an oral EZH2 inhibitor which has been FDA approved for adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies, and for adult patients with R/R FL who have no satisfactory alternative treatment option. We propose a study to evaluate the safety of tazemetostat in relapsed / refractory peripheral T-cell lymphoma.

Conditions

T-cell Lymphoma

Keywords

T-cell Lymphoma; Leukemia; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Identify the recommended phase II dose of Tazemetostat

  The measurement will be the occurrence of a dose limiting toxicity (DLT) in the first cycle (28 days) after treatment initiation from the start of cycle 1 day 1. Measurements will be graded on a Hematologic Toxicity scale from grades 1 through 4 with grade 4 being worst grade.

  28 days

Study Arms (1)

Cohort A

EXPERIMENTAL

T-cell Lymphomas

Drug: Tazemetostat

Interventions

Tazemetostat DRUG

Treatment: On day 1 and day 15 of the first cycle, and day 1 of all following cycles, the subject will have office visit with physical exam, vital signs, and lab tests. The subject will take tazemetostat twice a day by mouth continuously as an outpatient. If continuing on the treatment for more than 6 cycles, visits change to every 3 months.

Cohort A

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed peripheral T-cell lymphomas (PTCL) with allowed subtypes listed below as per the revised World Health Organization 2022 classification \[6\]:
• PTCL subtypes allowed
• PTCL-not otherwise specified (NOS)
• Nodal T-follicular helper cell lymphoma - angioimmunoblastic type, follicular type, or NOS
• Anaplastic Large Cell Lymphoma (ALK+)
• Anaplastic Large Cell Lymphoma (ALK-)
• Enteropathy-associated T-cell lymphoma
• Monomorphic epitheliotropic intestinal T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Adult T-cell leukemia / lymphoma - lymphomatous, acute, or unfavorable chronic subtypes
• Patients must have relapsed or refractory disease.
• Relapsed disease is defined when a patient progressed (\>3 months) after achieving CR with a previous treatment
• Refractory disease is defined when a patient failed to achieve a CR or PR after a previous treatment
• Patients received at least 1 prior therapy for PTCL.

You may not qualify if:

• Current evidence of central nervous system involvement.
• Completion of an autologous hematopoietic stem cell transplantation within 3 months prior to first dose of study drug.
• Prior allogeneic stem cell transplant within 6 months. The patient should not have any active GVH or should be on immune suppressive agents.
• Completion of treatment with any radiotherapy, chemotherapy, antibody, immunoconjugates and/or another investigational drug ≤4 weeks (or 5 half-lives of the drug, whichever is shorter) prior to first dose of study drug. Patients may be enrolled after a minimum of 2 weeks of radiation if radiation was for palliative intent.
• Prior therapy with an EZH2 inhibitor.
• Inability to swallow and retain oral medications.
• Pregnant women are excluded from this study.
• Any active, concurrent, significant illness or disease (other underlying lymphoma) or clinically significant findings including psychiatric and behavioral problems, medical history and/or physical examination findings that would preclude the patient from participation in the study such as:
• i. Active infection requiring systemic therapy ≤10 days before the first dose of study drug; ii. Unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association \[NYHA\] II, III, IV;), myocardial infarction ≤6 months prior to first study drug, uncontrolled cardiac arrhythmia e.g., atrial fibrillation/flutter, cerebrovascular accidents ≤6 months before first dose of study drug; iii. Any severe or uncontrolled other disease or condition which might increase the risk associated with study participation.
• Vaccination with live, attenuated vaccines within 28 days prior to the first dose of study medication.
• Receiving systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents). The use of inhaled corticosteroids is permitted.
• Corticosteroids ≥ 10 mg of prednisone within the last 7 days.
• Has had a solid organ transplant within the last 3 years. Note: Patients who have had a solid organ transplant \>3 years ago are eligible if there are no signs/symptoms of graft versus host disease (GvHD) and off immunosuppressive medications as per above.
• Any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN).
• Any prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL).

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Robert Award: collaborator
• Epizyme, Inc.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell; Leukemia; Lymphoma

Interventions

tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hematologic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 9, 2023
• Study Start: September 5, 2024
• Primary Completion: March 6, 2026
• Study Completion: March 6, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)