Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 1

Conditions: Follicular Lymphoma; Lymphoma, Non-Hodgkin; Diffuse Large B Cell Lymphoma

Treatments: Drug: Tazemetostat; Drug: Venetoclax

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05618366

22-04024678

Details and patient eligibility

About

The goal of this clinical trial is to learn about how a combination of tazemetostat and venetoclax in people with relapsed/refractory Non-Hodgkin Lymphoma (R/R NHL). The main questions that this trial aims to answer are what is the best dose of venetoclax to give with tazemetostat to people with R/R NHL; what types of side effects do people with R/R NHL get when taking venetoclax with tazemetostat; and what effects does this combination have on R/R NHL. Participants will need to take pills by mouth every day and regularly come to the clinic for blood work and imagining to monitor side effects and cancer progression. Participants may receive study drugs for up to 24 months.

Full description

This a phase 1, single arm, non-randomized trial of tazemetostat in combination with venetoclax in participants with two types of relapsed/refractory non-Hodgkin lymphoma. The purpose of this study is to evaluate the safety of the combination of tazemetostat and venetoclax in patients with relapsed/refractory (R/R) Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). This trial will be conducted in two parts. Part one will be a single-arm, open-label sequential dose escalation (3+3) of venetoclax in combination with a fixed dose of tazemetostat (800mg BID) to determine the maximum tolerated dose (MTD) of venetoclax. In part two, two expansion cohorts (R/R DLBCL and R/R FL) will be enrolled to further characterize the safety and tolerability of the combination, and to estimate the preliminary efficacy. Up to 18 participants will be enrolled in part 1 and 20 participants will be enrolled in part 2.

Enrollment: 38 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically confirmed, biopsy-proven diagnosis of FL or DLBCL.
• Subjects must have been treated with at least one prior line of therapy for lymphoma with evidence of disease progression.
• Subjects are eligible if they have progressed after ASCT OR if they are ineligible for ASCT

Exclusion criteria

• Significant cardiovascular impairment, such as history of congestive heart failure, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug
• Known hypersensitivity to any of the study drugs
• History of other cancer (some exceptions apply)
• Known CNS (brain or spinal cord) involvement at diagnosis
• Richter's transformation from CLL
• Evidence of uncontrolled systemic infection (viral, bacterial, or fungal)
• Major surgery within 3 weeks prior to the start of study treatment
• Venous thrombosis or pulmonary embolism within the last 3 months before starting study
• Uncontrolled infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1
• Pregnant or lactating (people capable of becoming pregnant or getting someone else pregnant must be willing to use highly effective birth control)
• Malabsorption syndrome or other condition that precludes enteral route of administration
• Inability to swallow tablets
• Known allergy to both xanthine oxidase inhibitors and rasburicase
• Clinically significant history of liver disease, including but not limited to viral or other hepatitis, current alcohol abuse, or cirrhosis
• Active hepatitis C (defined as a positive HCV viral load)
• Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer); chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index; or use of certain other prohibited medications
• Prior exposure to either tazemetostat or venetoclax
• Prior history of T-LBL/T-ALL
• Previous solid organ transplant
• Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
• Vaccination with live vaccines within 28 days prior to treatment
• Consumed grapefruit or grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

38 participants in 1 patient group

Tazemetostat and Venetoclax

Experimental group

Description:

All participants will receive a combination of oral 800 mg tazemetostat BID and oral venetoclax. Since this is a phase 1 trial, the dose of venetoclax will be determined by the investigators per a sequential dose escalation (3+3). Participants will be provided study drug in the form of pills to take at home. Study participants will need to regularly come to the clinic for blood work, imaging, and to monitor and side effects. Participants may receive study drug until their cancer progresses or for up to 24 months.

Treatment:

Drug: Venetoclax

Drug: Tazemetostat