Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma With EZH2 Gene Mutation

Eisai

Status and phase: Completed; Phase 2

Conditions: Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma

Treatments: Drug: Tazemetostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03456726

E7438-J081-206

Details and patient eligibility

About

This is a multicenter, open-label, Phase 2 study to assess the efficacy and safety of tazemetostat in participants with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) with EZH2 gene mutation.

Enrollment: 20 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma (NHL) as follows:

  • Cohort 1: Follicular lymphoma (FL)
  • Cohort 2: Diffuse large B-cell lymphoma (including primary mediastinal B-cell lymphoma and transformed FL)

• Participants who have confirmed EZH2 gene mutation of tumor in central laboratory

• Participants who have measurable disease

• Participants who had previous therapy with systemic chemotherapy and/or antibody therapy and for which no standard therapy exists

• Participants who had progressive disease or did not have response (complete response or partial response) in previous systemic therapy, or relapsed or progressed after previous systemic therapy

• Participants with Eastern Cooperative Oncology Group performance status of 0 to 1

• Participants with life expectancy of ≥3 months from starting study drug administration

• Participants with adequate renal, liver, and bone marrow function

• Male and female participants ≥20 years of age at the time of informed consent

• Participants who has provided written consent to participate in the study

Exclusion criteria

• Participants with prior exposure to EZH2 inhibitor

• Participants with a history or a presence of central nerves invasion

• Participants with malignant pleural effusion, cardiac effusion, or ascites retention

• Participants with allogeneic stem cell transplantation

• Participants with medical need for the continued use of potent inhibitors of Cytochrome P450 3A (CYP3A)or potent inducer of CYP3A (including St. John's wort)

• Participants with significant cardiovascular impairment

  · Participants with prolongation of corrected QT interval using Fridericia's formula to > 480 milliseconds (msec)

• Participants with venous thrombosis or pulmonary embolism within the last 3 months before starting study drug

• Participants with complications of hepatic cirrhosis, interstitial pneumonia or pulmonary fibrosis

• Participants with active infection requiring systemic therapy

• Women of childbearing potential or man of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception for periods from before informed consent to during the clinical study and 30 days later (for males 90 days later) from last administration of study drug

• Woman who are pregnant or breastfeeding

• Participants who were deemed as inappropriate to participate in the study by the investigator or sub-investigator

• Have any prior history of T-cell lymphoblastic lymphoma/T-cell acute lymphoblastic leukemia or myeloid malignancies, including myelodysplastic syndrome

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

FL with EZH2 gene mutation

Experimental group

Description:

Participants with follicular lymphoma (FL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 milligrams (mg) twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.

Treatment:

Drug: Tazemetostat

DLBCL with EZH2 gene mutation

Experimental group

Description:

Participants with diffuse large B-cell lymphoma (DLBCL) with the EZH2 gene mutation will receive oral tazemetostat at a starting dose of 800 mg twice daily (1600 mg total daily dose) by continuous regimen, no less than 8 hours between doses.

Treatment:

Drug: Tazemetostat