Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma
NCT ID: NCT05618366
Last Updated: 2025-04-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1
38 participants
INTERVENTIONAL
2023-06-07
2028-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Loncastuximab Tesirine and Venetoclax for Relapsed/ Refractory Non-Hodgkin Lymphoma
NCT05053659
Venetoclax and Romidepsin in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma
NCT03534180
A Study of TAK-659 in Combination With Venetoclax for Adult Participants With Previously Treated Non-Hodgkin Lymphoma
NCT03357627
Testing the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
NCT05627245
A Phase II Trial of Mosunetuzumab, Polatuzumab, Tafasitamab, and Lenalidomide in Patients With Relapsed B-cell NHL
NCT05615636
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
This trial will be conducted in two parts. 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) we will conduct a phase I trial in two parts. In part one, we will perform a single-arm, open-label sequential dose escalation (3+3) of venetoclax in combination with tazemetostat, given at its recommended phase II dose (RP2D) of 800mg BID, to determine the maximum tolerated dose (MTD) of venetoclax. In part two, we will enroll two expansion cohorts (R/R DLBCL and R/R FL) 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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Tazemetostat and Venetoclax
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.
Venetoclax
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.
Tazemetostat
Tazemetostat 800mg taken orally, twice daily.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Venetoclax
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.
Tazemetostat
Tazemetostat 800mg taken orally, twice daily.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. Adults aged ≥18
2. Require therapy as determined by the treating physician
3. 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
4. ECOG PS 0-2
5. Ability and willingness to provide signed Informed Consent Form
6. Ability and willingness to comply with the requirements of the study protocol
7. 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:
1. Histologically confirmed, biopsy-proven diagnosis of DLBCL (as determined by WHO standard classification criteria).
Please note: Transformed DLBCL patients are eligible, with the exception of Richter's transformation.
2. Subjects must have received at least two prior lines of therapy for lymphoma with evidence of disease progression.
3. Subjects are eligible if they have progressed after ASCT OR if they are ineligible for ASCT, as determined by their treating physician.
R/R FL Cohort:
1. Histologically confirmed, biopsy-proven diagnosis of FL
2. Subjects are eligible if they have progressed after two or more lines of therapy for lymphoma or have no satisfactory treatment alternatives
Exclusion Criteria
1. 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.
2. Known hypersensitivity to any of the study drugs
3. 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.
4. Known CNS involvement at diagnosis (CNS evaluation not required in the absence of clinical suspicion)
5. Richter's transformation from CLL
6. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
7. Major surgery within 3 weeks prior to the start of study treatment
8. 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.
9. Uncontrolled infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1
10. Pregnant or lactating
11. 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
12. 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:
13. Inability to swallow tablets
14. Known allergy to both xanthine oxidase inhibitors and rasburicase
15. Clinically significant history of liver disease, including but not limited to viral or other hepatitis, current alcohol abuse, or cirrhosis Note: Subjects with positive HBV core antibody or surface antigen are eligible as long as they have an undetectable HBV DNA PCR and are willing to undergo monthly DNA testing, and receive concurrent antiviral therapy with entecavir, tenofovir, or lamivudine, and continued for a minimum of 6 months after completion of therapy.
16. Active hepatitis C (defined as a positive HCV viral load)
17. Chronic use of moderate or strong CYP3A4 modulators (inhibitor or inducer) or any other prohibited medications. A washout period of 5 half-lives or 14 days, whichever is longer, is required prior to venetoclax or tazemetostat dosing if a prohibited medication is discontinued.
18. Chronic use of a P-gp inhibitor, or a P-gp substrate with a narrow therapeutic index (see Section 7.8). A washout period of 5 half-lives or 14 days, whichever is longer is required prior to venetoclax or tazemetostat dosing if a prohibited medication is discontinued.
19. Prior exposure to either tazemetostat or venetoclax
20. Has a prior history of T-LBL/T-ALL
21. Subjects who have undergone a solid organ transplant
22. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in this study OR interfere with their ability to receive study treatment or complete the study.
23. Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
24. Vaccination with live vaccines within 28 days prior to treatment
25. 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Genentech, Inc.
INDUSTRY
Epizyme, Inc.
INDUSTRY
Weill Medical College of Cornell University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Lisa Roth, M.D.
Role: PRINCIPAL_INVESTIGATOR
Weill Medical College of Cornell University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Weill Cornell Medicine/NewYork-Presberteryian Hospital
New York, New York, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
22-04024678
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.