Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma

NCT05618366 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 22-04024678
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Maximum-tolerated dose (MTD) determination (Part 1)

  In part 1 of this study, participants will be assigned a dose of venetoclax following a (3+3) dose escalation design and monitored for dose-limiting toxicities (DLTs) during the first treatment cycle. Based on observed DLTs observed in each dose level cohort, the maximum-tolerated dose will be determined. The # of patients experiencing a DLT among the evaluable patients for each dose level in part 1 will be tabulated.

  Day 0 to 28

• Number of participants who experience dose-limiting toxicities (DLTs)

  In part 1 of this study, participants will be assigned a dose of venetoclax following a (3+3) dose escalation design and monitored for dose-limiting toxicities (DLTs) during the first treatment cycle. Dose limiting toxicity (DLT) will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

  Day 0 to 28

• Number of participants who experience adverse events (AEs), from baseline to 30 days after the last dose of study drug, as assessed by CTCAE v5.0

  The safety analysis population will consist of all enrolled patients who receive at least one dose of study drug. AEs and SAEs will be tabulated by type, grade, and attribution for all patients overall and by treatment group. For each patient, and within each type of toxicity, the patient will be counted only once at the highest grade of that toxicity. Participants will be evaluated for AEs/SAEs from the time they sign the informed consent form until 30 days after their last dose of study drug.

  Baseline through 25 months

• Number of adverse events (AEs) by severity from baseline to 30 days, after the last dose of study drug as assessed, by CTCAE v5.0

  The safety analysis population will consist of all enrolled patients who receive at least one dose of study drug. AEs and SAEs will be tabulated by type, grade, and attribution for all patients overall and by treatment group. For each patient, and within each type of toxicity, the patient will be counted only once at the highest grade of that toxicity. Participants will be evaluated for AEs/SAEs from the time they sign the informed consent form until 30 days after their last dose of study drug.

  Baseline through 25 months

Secondary Outcomes (7)

• Number of Participants who Achieve Complete Response (CR)

  Day 0 through 24 months

• Number of Participants who Achieve Partial Response (PR)

  Day 0 through 24 months

• Overall Response Rate (ORR)

  Day 0 through 24 months

• Duration of Response (DoR)

  From date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, as assessed at 5 years

• Progression-Free Survival

  From date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, as assessed at 5 years

Study Arms (1)

Tazemetostat and Venetoclax

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Tazemetostat

Interventions

Venetoclax DRUG

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.

Also known as: Venclexta

Tazemetostat and Venetoclax

Tazemetostat DRUG

Tazemetostat 800mg taken orally, twice daily.

Also known as: Tazverik

Tazemetostat and Venetoclax

Eligibility Criteria

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

You may qualify if:

• Patients must meet the following criteria for study entry:
• Adults aged ≥18
• Require therapy as determined by the treating physician
• Patients must have adequate organ and bone marrow function:
• Absolute neutrophil count (ANC) ≥ 1 x 109/L without growth factor support (filgrastim or pegfilgrastim) for at least 14 days
• Platelet count ≥75 x 109/L, evaluated at least 7 days after last platelet transfusion
• Hemoglobin ≥9.0g/dL, independent of transfusion
• Total bilirubin \< 1.5 x's the upper limit of the normal range (ULN), except Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x's ULN.
• Calculated creatinine clearance according to the Cockcroft-Gault equation. ≥ 40 mL/min
• ECOG PS 0-2
• Ability and willingness to provide signed Informed Consent Form
• Ability and willingness to comply with the requirements of the study protocol
• Measurable disease (defined as ≥ 1.5cm in diameter) In addition, patients must meet the following conditions for enrollment based on whether they have DLBCL or FL.
• R/R DLBCL Cohort:

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from study entry:
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia.
• Known hypersensitivity to any of the study drugs
• History of other malignancy that could affect compliance with the protocol or interpretation of results
• a. Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for 2 years prior to enrollment.
• Known CNS involvement at diagnosis (CNS evaluation not required in the absence of clinical suspicion)
• Richter's transformation from CLL
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, 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; whereas subjects greater than 3 months since deep vein thrombosis/pulmonary embolism are eligible but are recommended to receive prophylaxis.
• Uncontrolled infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1
• Pregnant or lactating
• Patients capable of becoming pregnant or getting someone else pregnant must be willing to use highly effective birth control as described in Section 4.4
• Malabsorption syndrome or other condition that precludes enteral route of administration Patients who meet any of the following criteria will be excluded from study entry:
• Inability to swallow tablets

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Genentech, Inc.: collaborator
• Epizyme, Inc.: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presberteryian Hospital

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

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

Interventions

venetoclax; tazemetostat

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Study Officials

• Erin Mulvey, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 16, 2022
• Study Start: June 7, 2023
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)