Brentuximab + Bendamustine for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Joseph Tuscano
Must not be taking: Immunosuppressants, Antibiotics, others
Disqualifiers: CNS involvement, Severe infections, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial investigates how well brentuximab vedotin and bendamustine work in treating patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to determine if the combination of brentuximab vedotin plus bendamustine is safe and to determine the effectiveness of the combination.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy or radiotherapy must be stopped at least 2 weeks before starting the trial, and herbal therapies require a 1-week washout period (time without taking them). Please consult with the trial team for guidance on your specific medications.
What data supports the effectiveness of the drug combination Brentuximab and Bendamustine for treating follicular lymphoma?
Bendamustine, when combined with rituximab, has shown high effectiveness in treating indolent lymphomas, including follicular lymphoma, with good response rates and the ability to eradicate minimal residual disease. This suggests that Bendamustine is effective in similar lymphoma treatments, which may support its use in combination with Brentuximab for follicular lymphoma.
12345Is the combination of Brentuximab and Bendamustine safe for humans?
Bendamustine has been studied in patients with non-Hodgkin lymphoma, and it was generally well-tolerated with no significant increase in adverse events when used with anti-nausea medications. However, specific safety data for the combination of Brentuximab and Bendamustine in humans is not provided in the available research.
678910How does the drug combination of Brentuximab Vedotin and Bendamustine differ from other treatments for follicular lymphoma?
The combination of Brentuximab Vedotin and Bendamustine is unique because it targets follicular lymphoma by combining a targeted therapy (Brentuximab Vedotin) with a chemotherapy agent (Bendamustine), potentially offering a novel approach for patients who have not responded to other treatments. This combination has shown promise in treating other types of lymphoma, such as Hodgkin lymphoma, suggesting it may offer benefits for follicular lymphoma as well.
24111213Eligibility Criteria
This trial is for adults with relapsed or refractory follicular lymphoma, a type of non-Hodgkin lymphoma. Participants must have had at least one prior treatment, measurable disease via scans, and be generally healthy with proper organ function. They should not be pregnant and agree to use contraception. Those with recent infections, certain allergies, severe liver disease, uncontrolled illnesses or who've recently used similar drugs are excluded.Inclusion Criteria
Hemoglobin >= 8 g/dL
Absolute neutrophil count >= 1,000/mcL
Platelets >= 50,000/mcL
+17 more
Exclusion Criteria
You have a known allergy or sensitivity to products made from Chinese hamster ovary cells or other human antibodies made in a laboratory.
I have not had signs of infection in the last 2 weeks.
I have taken a one-time low dose of medication to suppress my immune system.
+26 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive brentuximab vedotin and bendamustine intravenously. Treatment repeats every 21 days for 6 cycles.
18 weeks
6 visits (in-person)
Extension
Participants who respond to treatment may continue to receive single-agent brentuximab vedotin for up to 10 additional cycles.
30 weeks
10 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
2 years
Every 3 months
Participant Groups
The trial tests the combination of brentuximab vedotin (a monoclonal antibody linked to a toxin) and bendamustine (a chemotherapy drug) in patients whose follicular lymphoma has returned or resisted treatment. The goal is to see if this combo is safe and effective in stopping cancer growth by targeting cancer cells directly while preventing them from dividing or spreading.
1Treatment groups
Experimental Treatment
Group I: Treatment (brentuximab vedotin, bendamustine)Experimental Treatment2 Interventions
Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.
Bendamustine Hydrochloride is already approved in United States, European Union, Japan for the following indications:
🇺🇸 Approved in United States as Treanda for:
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin lymphoma (NHL)
🇪🇺 Approved in European Union as Levact for:
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin lymphoma (NHL)
- Multiple myeloma
🇯🇵 Approved in Japan as Ribomustin for:
- Chronic lymphocytic leukemia (CLL)
- Non-Hodgkin lymphoma (NHL)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California Davis Comprehensive Cancer CenterSacramento, CA
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Who Is Running the Clinical Trial?
Joseph TuscanoLead Sponsor
National Cancer Institute (NCI)Collaborator
Seagen Inc.Industry Sponsor
References
Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. [2022]To determine the efficacy and safety of bendamustine as a single agent in refractory or relapsed T-cell lymphomas.
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: a review of its use in the management of indolent non-Hodgkin lymphoma. [2021]Bendamustine (Treanda, Ribomustin) is a bifunctional alkylating agent that also has potential antimetabolite properties, and only partial cross-resistance occurs between bendamustine and other alkylators. In patients with indolent non-Hodgkin lymphoma (NHL), bendamustine monotherapy achieved high objective response rates in those with rituximab-refractory disease in a pivotal noncomparative trial and a similarly designed smaller phase II study. Many of these heavily treated patients were also refractory to standard chemotherapy regimens. Several phase II trials demonstrated good response rates with single-agent bendamustine, or bendamustine in combination with rituximab, in patients with indolent NHL whose disease relapsed after (or was refractory to) chemotherapy. Phase III studies comparing combination regimens as first-line therapy in patients with indolent NHL showed no significant differences in response rates between bendamustine-containing regimens and standard regimens included in treatment guidelines. Bendamustine has been generally well tolerated in clinical trials and has a low propensity to induce alopecia. Results of ongoing trials will help to clarify the optimal role of bendamustine in indolent NHL. Available data indicate that it may be a particularly useful treatment option as monotherapy in patients with indolent NHL whose disease progressed during or following rituximab-based therapy, many of whom are also refractory to standard chemotherapy regimens.
The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study. [2023]R-Bendamustine is an effective treatment for follicular lymphoma (FL). Previous large trials demonstrated the prognostic role of the molecular minimal residual disease (MRD) during the most frequently adopted chemotherapeutic regimens, but there are not yet conclusive data about the effect of combination of rituximab (R) and bendamustine in terms of MRD clearance. Thus, the aim of this retrospective study was to assess if and in what extent the combination of rituximab and bendamustine would exert a significant reduction of the molecular disease in 48 previously untreated FL patients. The molecular marker at baseline was found in the 62.5% of cases; no significant differences were observed between patients with or without the molecular marker in respect of the main clinical features. Moreover, the quantization of the baseline molecular tumor burden showed a great variability: the median value was 1.4 × 10-2 copies, ranging from 3 × 10-5 to 4 × 104. The initial molecular tumor burden did not correlate with clinical features and did not impact on the subsequent quality of response. After treatment, 93% of cases became MRD-negative; the median reduction of the BCL2/JH load was 4 logs. The 2-years PFS was 85%; it was significantly longer for patients in complete than for those in partial response (91 vs. 57%; p = 0.002), and for cases with lower FLIPI-2 score (88 vs. 60%; p = 0.004). On the contrary, PFS did not differ between patients with or without the molecular marker at baseline; a molecular tumor burden 15 times higher was observed in the relapsed subgroup in comparison to the relapse-free one, but this difference did not change the PFS length. The 2-years OS was 93.6%; the only variable that significantly impacted on it was the FLIPI-2 score; the presence of the molecular marker at baseline or its behavior after treatment did not impact on survival. This study, even if retrospective and conducted on a small series of patients, would represent a proof of concept that R-bendamustine is able to so efficaciously eradicate MRD that it could be able to by-pass the prognostic significance of MRD already demonstrated for other chemotherapeutic regimens in FL.
Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance). [2020]This multicenter, randomized phase 2 trial evaluated complete responses (CRs), efficacy, and safety with ofatumumab and bendamustine and with ofatumumab, bendamustine, and bortezomib in patients with untreated, high-risk follicular lymphoma (FL).
Rolapitant (Varubi): A Substance P/Neurokinin-1 Receptor Antagonist for the Prevention of Chemotherapy-Induced Nausea and Vomiting. [2020]Rolapitant (Varubi) for the prevention of chemotherapy-induced nausea and vomiting.
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.
Safety and efficacy of netupitant/palonosetron and dexamethasone in classical Hodgkin's lymphoma patients with inadequate chemotherapy-induced nausea and vomiting prophylaxis with palonosetron and dexamethasone: a single-center real-life experience. [2020]We analyzed safety of NEPA (netupitant/palonosetron) and dexamethasone (NEPA+DEX) for the management of chemotherapy-induced nausea and vomiting (CINV) in classical Hodgkin's lymphoma patients that experienced CINV with a prophylaxis with palonosetron (PALO + DEX). In a retrospective, monocentric, noncomparative study, we analyzed adverse events and CINV grading in patients who switched from PALO + DEX to NEPA + DEX. Among 32 patients treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) during the study period, 47% did not properly control CINV with PALO + DEX and were shifted to NEPA + DEX. Among these, 53.3% properly controlled CINV is for all the remaining chemotherapy cycles. We did not observe an increase of adverse events after switching to NEPA. In our study, NEPA did not show drug-drug interaction with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy agents and NEPA administration was well tolerated with mild and transient adverse events.
Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. [2019]The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.
[Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. [2008]The efficiency of antiemetic drugs was investigated in 36 children with neoplasia (mainly of hematopoietic system) in the course of 83 cycles of chemotherapy. The following antiemetic drugs were investigated: Fenactil (brand of chlorpromazine), Torecan (brand of thienylpromazine maleate), Aviomarin (brand of dimenhydrinate), Decadron (brand of dexamethasone), Primperan (brand of metoclopramid), and placebo. The most efficient was dexamethasone which prevented vomiting in 54% cycles of chemotherapy and diminished their intensity in the remaining cycles. No adverse reactions were noted. Efficacy of Fenactil, Torecan, Aviomarin, and Primperan was similar to that of placebo.
Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma. [2015]Although bendamustine plus rituximab has demonstrated efficacy in indolent B cell non-Hodgkin's lymphoma (B-NHL), data for this combination in aggressive B-NHL are extremely limited. The present dose-escalation study evaluated the safety, efficacy, and pharmacokinetics of bendamustine hydrochloride in combination with rituximab in patients with relapsed/refractory, CD20-positive, aggressive B-NHL. Patients received rituximab 375 mg/m(2) , i.v., on Day 1 and bendamustine at either 90 (Cohort 1) or 120 mg/m(2) (Cohort 2), i.v., on Days 2 and 3 of a 21-day cycle. The primary endpoint was the proportion of patients experiencing dose-limiting toxicity (DLT). Secondary endpoints were adverse events (AE), the overall response rate (ORR), and pharmacokinetic parameters. Nine patients received rituximab plus bendamustine: three in Cohort 1 and six in Cohort 2. Histologies included diffuse large B cell lymphoma (n = 5), mantle cell lymphoma (n = 2), and transformed lymphoma (n = 2). No DLT was observed at either dose level. Grade 3/4 hematologic AE included lymphocytopenia, leukocytopenia, and neutropenia (n = 9 each; 100%), and thrombocytopenia (n = 2; 22%). No Grade 3/4 gastrointestinal AE were reported. The ORR was 33% (one partial response) in Cohort 1 and 100% (five complete and one partial response) in Cohort 2. The maximum drug concentration and area under the blood concentration-time curve for bendamustine increased dose dependently, with time to maximum blood concentration = 1.0 h in both cohorts; these pharmacokinetic data were similar to those reported previously for single-agent bendamustine in patients with indolent B-NHL. In conclusion, bendamustine 120 mg/m(2) plus rituximab 375 mg/m(2) was feasible and generally well tolerated, with promising efficacy in relapsed or refractory aggressive B-NHL.
Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. [2020]Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.
Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed.