Tazemetostat + Rituximab + Bendamustine for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Vaishalee Kenkre
Must not be taking: CYP3A4/5 inhibitors
Disqualifiers: Active infection, Concurrent malignancy, CNS metastases, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This study is planned as a single arm clinical trial of tazemetostat in combination with bendamustine and rituximab with both a phase I and phase II component. All patients will receive tazemetostat twice daily on days 1-28 in combination with bendamustine 90 mg/m2 IV on days 1 and 2 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles. Following this, patients will receive tazemetostat twice daily on days 1-28 and rituximab 375 mg/m2 IV on day 1 of a 28-day cycle for up to three cycles.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you require chronic use of certain drugs that affect liver enzymes (CYP3A4/5 inhibitors or inducers) within 28 days before starting the trial.
What data supports the effectiveness of the drug combination Tazemetostat, Rituximab, and Bendamustine for treating follicular lymphoma?
Research shows that the combination of Bendamustine and Rituximab is effective in treating various types of indolent lymphomas, including follicular lymphoma, with high response rates and manageable side effects. Although Tazemetostat is not specifically mentioned in these studies, its inclusion in the treatment may enhance effectiveness based on its known properties.
12345What safety data exists for Bendamustine in combination with Rituximab for treating lymphoma?
Bendamustine has been studied for its safety and effectiveness in patients with certain types of lymphoma, showing it can be effective, but the study also evaluated its toxicity (side effects).
678910What makes the drug combination of Tazemetostat, Rituximab, and Bendamustine unique for treating follicular lymphoma?
This drug combination is unique because it includes Tazemetostat, which is an EZH2 inhibitor that targets specific genetic mutations in cancer cells, potentially enhancing the effectiveness of Rituximab and Bendamustine, which are already known to be effective in treating various lymphomas. This combination may offer a novel approach by targeting cancer cells more precisely, potentially improving outcomes for patients with follicular lymphoma.
34111213Eligibility Criteria
Adults with high tumor burden follicular lymphoma, grades 1-2 or 3A, who haven't had certain prior treatments can join. They must have good organ function and no history of severe heart disease, active infections, other cancers in the last 3 years (with some exceptions), CNS metastases, uncontrolled HIV/AIDS or hepatitis C.Inclusion Criteria
I am 18 years old or older.
I have been active and mostly self-sufficient in the last 10 days.
My cancer is at stage II, III, or IV according to the Ann Arbor system.
+7 more
Exclusion Criteria
I do not have active brain metastases or leptomeningeal disease.
I do not have an active infection needing treatment within 4 weeks of starting the study drug.
Treatment with any investigational drug within 4 weeks prior to registration.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Phase I Treatment
Participants receive tazemetostat with bendamustine and rituximab for up to 3 cycles. Dose escalation of tazemetostat is conducted to determine the recommended Phase 2 dose.
12 weeks
3 visits (in-person) per cycle
Phase II Treatment
Participants receive tazemetostat and rituximab for up to 3 additional cycles at the recommended Phase 2 dose.
12 weeks
3 visits (in-person) per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 years
Participant Groups
The trial tests Tazemetostat combined with Bendamustine and Rituximab for untreated high-burden follicular lymphoma. It's a two-phase study where all patients get these drugs in cycles: first three cycles include all three drugs; next three just Tazemetostat and Rituximab.
1Treatment groups
Experimental Treatment
Group I: Investigational GroupExperimental Treatment3 Interventions
Phase 1:
90 mg/m\^2 of bendamustine by IV on Day 1 and 2 of a 28 day cycle (up to 3 Cycles)
375 mg/m\^2 of rituximab by IV on Day 1 of a 28 day cycle (up to 3 Cycles)
Participants enrolled in this phase will be given one of 3 different dose levels of tazemetostat along with the drugs above (for up to 3 Cycles). 3 patients will be assigned to the lowest dose level and if the dose is tolerated, 3 more patients will be enrolled one dose level higher. Up to 18 participants being enrolled.
Dose Level 1: 400 mg of tazemetostat orally twice daily
Dose Level 2: 600 mg of tazemetostat orally twice daily
Dose Level 3: 800 mg of tazemetostat orally twice daily
Phase 2:
6 patients from Phase 1 who were treated at the recommended Phase 2 dose will be added to 21 additional patients.
375 mg/m\^2 of rituximab through IV on Day 1 of a 28 day cycle (Cycles 1-6)
Tazemetostat orally twice daily of a 28 day cycle (Cycles 1-6)
Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Treanda for:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
🇪🇺 Approved in European Union as Ribomustin for:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
- Multiple myeloma
🇨🇦 Approved in Canada as Levact for:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
🇯🇵 Approved in Japan as Bendamustine hydrochloride for:
- Chronic lymphocytic leukemia
- Non-Hodgkin lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Northwestern UniversityChicago, IL
University of Wisconsin Carbone Cancer CenterMadison, WI
University of Illinois Cancer CenterChicago, IL
Rutgers Cancer Institute of New JerseyNew Brunswick, NJ
More Trial Locations
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Who Is Running the Clinical Trial?
Vaishalee KenkreLead Sponsor
Epizyme, Inc.Industry Sponsor
University of Wisconsin, MadisonCollaborator
References
Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]We aimed to investigate the efficacy and side effects of bendamustine in relapsed/refractory lymphoma patients in Turkey.
Bendamustine-rituximab regimen in untreated indolent marginal zone lymphoma: experience on 65 patients. [2020]First line therapy of patients with marginal zone lymphomas (MZL) is not well established and various regimens with chemo-immunotherapy can be used. Rituximab plus bendamustine (BR) is an effective and manageable treatment option for patients affected by indolent non-Hodgkin lymphoma. The aim of this monocentric retrospective study was to analyze the effectiveness and safety of the use of BR regimen in MZL patients in first line in daily clinical practice. The treatment schedule was rituximab at the dose of 375 mg/m2 on day 1 of each cycle and bendamustine at the dose of 90 mg/m2 on day 2 and 3, every 28 days for a maximum of 6 cycles. We analyzed 65 MZL patients (28 extranodal [EMZL], 23 splenic [SMZL], and 14 nodal [NMZL]) who underwent BR regimen as first line treatment. The median time from diagnosis to therapy was 2.5 months. Final responses were: 38 complete response (CR, 58.5%), 20 partial response and 7 progressive disease, leading to an overall response rate (ORR) of 89.2%. With respect to the histology, the ORR was 89.3% for EMZL, 82.6% for SMZL and 100% for NMZL, respectively (difference not statistically significant). With a median follow-up time of 44.6 months (range, 3.3-175.0 months), 2 (one EMZL after 42 months and one SMZL after 10 months) of 38 (5.2%) CR patients had disease relapse, yielding an estimated disease free survival of 89.2% at 61.1 months. The estimated 6-year progression free survival was 71.8% with 15 relapsed/progressed patients showing lymphoma recurrence within 48 months from end of treatment. The most frequently reported adverse events (any grade) were neutropenia (N = 35, 53.8%), fatigue (N = 15, 23.0%), and nausea (N = 12, 18.4%). All toxicities quickly resolved and no treatment-related death occurred. The BR regimen is effective and feasible in MZL patients inducing prolonged disease control with manageable toxicities.
Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. [2015]Bendamustine is a water-soluble, bifunctional chemotherapeutic agent with characteristics of both an alkylator and a purine analog. Bendamustine combined with rituximab in vitro shows synergistic effects against various leukemia and lymphoma cell lines. Clinical trials supporting these results show that bendamustine plus rituximab is highly effective in relapsed and refractory patients with indolent lymphoma. The results have been found in rituximab-naive, rituximab-pretreated, and rituximab-refractory patients with excellent response rates and toxicity profiles. Bendamustine is effective both with rituximab and as a monotherapy in rituximab-refractory patients. Interim results from a phase III, randomized trial comparing bendamustine and rituximab to a standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and rituximab regimen suggest that combination bendamustine and rituximab may provide a viable alternative for treatment of many indolent lymphomas.
Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study. [2019]The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.
Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin's lymphoma. [2021]Bendamustine is an alkylating agent which also shows properties of a purine analog. Because of its unique mechanism of action it shows activity in relapsed indolent lymphomas which are resistant to alkylating agents, purine analogs, and rituximab. Bendamustine has a favorable toxicity profile causing no alopecia and only a moderate hematotoxicity and gastrointestinal toxicity. Combinations of bendamustine with mitoxantrone and rituximab and with rituximab alone have been shown to be highly active in relapsed/refractory indolent lymphomas and mantle cell lymphomas achieving long lasting complete remissions. Because of only moderate toxicity these combinations can be applied safely in elderly patients who can be treated in an outpatient setting.
Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. [2021]Bendamustine hydrochloride is a novel alkylating agent. In this multicenter study, the authors evaluated the efficacy and toxicity of single-agent bendamustine in patients with rituximab-refractory, indolent B-cell lymphoma.
Efficacy and tolerability of tropisetron in the prevention of cisplatin-induced nausea and vomiting in advanced non-small cell lung cancer. [2019]The efficacy and tolerability of tropisetron were studied in an open trial comprising a total of 30 patients with advanced non-small cell lung cancer undergoing high-dose, cisplatin-based chemotherapy (cisplatin dosage 100 mg/m2). Patients received tropisetron 5 mg intravenous infusions for 15 min on day 1. followed by 5 mg tropisetron taken orally in the morning on days 2 6. All treated patients were assessed during the entire treatment period (6 days). Acute nausea and vomiting were evaluated during the 24 h after chemotherapy. Delayed nausea and vomiting were evaluated during days 2-6 after chemotherapy. Response to tropisetron was graded as: complete control, major control, minor control and failure for nausea or vomiting. Rates for complete plus major control of acute nausea and vomiting in cycles 1-5 were 77%, 81%, 86%, 67% and 75%, respectively. Rates for complete plus major control of delayed nausea and vomiting in cycles 1-5 were 87%, 76%, 86%, 78% and 75%, respectively. Adverse reactions were mainly headache and diarrhea, but both reactions were mild and are common in most patients treated with this type of antiemetic agent. It is concluded that tropisetron is an effective drug for the prevention of side effects of highly emetogenic drugs such as cisplatin. The dosage and schedule of tropisetron reported here can prevent both acute and delayed nausea and vomiting.
Prevention of emesis by tropisetron (Navoban) in children receiving cytotoxic therapy for solid malignancies. [2018]Emesis is one of the most frequent and distressing adverse effects of cytotoxic chemotherapy. Conventional antiemetic regimens are unsatisfactory due to their poor efficacy and their adverse events, particularly in children. Tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) belongs to a new class of 5-hydroxytryptamine receptor antagonists with antiemetic effectiveness in patients receiving anticancer agents. We evaluated tropisetron (0.2 mg/kg/d) in 24 chemotherapy-treated children who had experienced severe emesis during previous chemotherapy courses in spite of concomitant administration of either alizapride or metoclopramide. Complete control of emesis was achieved in 70% of the courses (37% of those including cisplatin). No severe adverse effect was reported. Headache was observed in two courses and constipation was observed during two other courses. Tropisetron proved clearly superior to conventional antiemetics and safe in use.
A report comparing the use of tropisetron (Navoban), a 5-HT3 antagonist, with a standard antiemetic regimen of dexamethasone and metoclopramide in cisplatin-treated patients under conditions of severe emesis. [2018]This report of a double-blind, randomized study performed to evaluate the comparative antiemetic efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), a new 5-hydroxytryptamine receptor antagonist, focuses on treatment during stages of chemotherapy when nausea and vomiting are particularly severe. One hundred fifteen chemotherapy-naive patients with malignant disease were administered either tropisetron (n = 58) or a dexamethasone dose plus a metoclopramide dose (n = 57) during 5 days of two successive cycles of chemotherapy. Within the first 24 hours after receiving cisplatin-based chemotherapy, 76% of patients in the tropisetron group remained free of vomiting (with 59% of patients free of nausea) compared with 39% of patients free of vomiting in the conventionally treated group (30% of patients free of nausea). Improved control of emesis also was observed over 4 consecutive days of follow-up in the tropisetron group. The difference in incidence of nausea and vomiting between the patient groups was statistically significant (P
Tropisetron alone or in combination with dexamethasone for the prevention and treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial. [2019]This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.
An evaluation of the potential for drug-drug interactions between bendamustine and rituximab in indolent non-Hodgkin lymphoma and mantle cell lymphoma. [2021]Bendamustine plus rituximab has been reported to be effective in treating lymphoid malignancies. This analysis investigated the potential for drug-drug interactions between the drugs in patients with indolent non-Hodgkin lymphoma or mantle cell lymphoma.
Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. [2019]Rituximab plus bendamustine (R-B) has been demonstrated to improve outcomes and reduce toxicity compared with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) in follicular lymphoma (FL). Nevertheless, in clinical practice, many centers still prefer R-CHOP to R-B in patients with FL grade 3A (FL3A). Therefore, we retrospectively assessed patients with FL3A treated with either R-CHOP or R-B in five European cancer centers and compared their outcomes.
Navitoclax (ABT-263) and bendamustine ± rituximab induce enhanced killing of non-Hodgkin's lymphoma tumours in vivo. [2021]Bendamustine with or without rituximab provides an effective and more tolerable alternative to the polytherapy cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) in the treatment of haematological tumours and is currently approved for the treatment of many haematological malignancies. Navitoclax (ABT-263) is a potent inhibitor of Bcl-2, Bcl-x(L) and Bcl-w, which has demonstrated efficacy in haematological tumours alone and in combination with other agents. This paper describes the in vivo efficacy of combining either bendamustine or bendamustine plus rituximab (BR) with navitoclax in xenograft models of non-Hodgkin's lymphoma