Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

Trial Title: Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

NCT ID: NCT05618366

Condition: Lymphoma, Non-Hodgkin
Diffuse Large B Cell Lymphoma
Follicular Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Venetoclax

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Venetoclax
Description: Participants will receive oral venetoclax taken once per day. The dose will be between 200 and 800 mg daily, with the exact dose determined by the protocol.
Arm group label: Tazemetostat and Venetoclax

Other name: Venclexta

Intervention type: Drug
Intervention name: Tazemetostat
Description: Tazemetostat 800mg taken orally, twice daily.
Arm group label: Tazemetostat and Venetoclax

Other name: Tazverik

Summary: 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.

Detailed 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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Weill Cornell Medicine/NewYork-Presberteryian Hospital

Address:
City: New York
Zip: 10021
Country: United States

Status: Recruiting

Contact:
Last name: Tejasvi Kaur Sahni

Phone: 646-962-9337
Email: tks4001@med.cornell.edu

Contact backup:
Last name: Brittany Hobbie
Email: brh4008@med.cornell.edu

Investigator:
Last name: Lisa Roth, M.D.
Email: Principal Investigator

Start date: June 7, 2023

Completion date: December 2028

Lead sponsor:
Agency: Weill Medical College of Cornell University
Agency class: Other

Collaborator:
Agency: Genentech, Inc.
Agency class: Industry

Collaborator:
Agency: Epizyme, Inc.
Agency class: Industry

Source: Weill Medical College of Cornell University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05618366