Tazemetostat and Venetoclax in Relapsed/Refractory Non-Hodgkin Lymphoma
- Conditions
- Interventions
- Registration Number
- NCT05618366
- Lead Sponsor
- Weill Medical College of Cornell University
- 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 ...
- 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 ...
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 38
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tazemetostat and Venetoclax 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. Tazemetostat and Venetoclax Tazemetostat 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.
- Primary Outcome Measures
Name Time Method Maximum-tolerated dose (MTD) determination (Part 1) Day 0 to 28 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 evalua...
Number of participants who experience dose-limiting toxicities (DLTs) Day 0 to 28 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...
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 Baseline through 25 months 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. Parti...
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 Baseline through 25 months 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. Parti...
- Secondary Outcome Measures
Name Time Method Number of Participants who Achieve Complete Response (CR) Day 0 through 24 months CR will be assessed for all evaluable patients in parts 1+2 according to Lugano response criteria.
Number of Participants who Achieve Partial Response (PR) Day 0 through 24 months PR will be assessed for all evaluable patients in parts 1+2 according to Lugano response criteria.
Overall Response Rate (ORR) Day 0 through 24 months The ORR response rate is the proportion of patients with a best overall response of either complete response (CR) or partial response (PR) among all evaluable patients. ORR, CR, and PR will be assessed for all evaluable patients in parts 1+2 according to Lugano response criteria. The best overall response is the best response recorded from the start of treat...
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 The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or PD is objectively documented (taking as reference for PD the smallest measurements recorded since the treatment started).
...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 PFS is defined as the duration of time from start of treatment to time of documentation of progression or death from any cause.
Overall Survival (OS) From date of treatment initiation until the date of death from any cause, as assessed at 5 years OS is defined as the duration of time from start of treatment to death from any cause.
Mean Change in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score from Baseline to End of Treatment Baseline; at the start of Cycle 4 (a cycle is 28 days); at the start of Cycle 7; and End of Treatment (treatment will continue until disease progression or unacceptable toxicity for a maximum of approximately 2 years) FACT-Lym is a 42 item questionnaire that includes questions on physical well-being, social/family well-being, emotional well-being, functional well-being, and lymphoma symptoms over the past 7 days. Each response is measured on a 5 point Likert-type scale. Scores can range from 0 to 168 with higher scores indicating better quality of life.
Trial Locations
- Locations (1)
Weill Cornell Medicine/NewYork-Presberteryian Hospital
🇺🇸New York, New York, United States